start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=
article-no=
start-page=1371307
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240528
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Dissection of the signal transduction machinery responsible for the lysyl oxidase-like 4-mediated increase in invasive motility in triple-negative breast cancer cells: mechanistic insight into the integrin-β1-NF-κB-MMP9 axis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Triple-negative breast cancer (TNBC) cells are a highly formidable cancer to treat. Nonetheless, by continued investigation into the molecular biology underlying the complex regulation of TNBC cell activity, vulnerabilities can be exposed as potential therapeutic targets at the molecular level. We previously revealed that lysyl oxidase-like 4 (LOXL4) promotes the invasiveness of TNBC cells via cell surface annexin A2 as a novel binding substrate of LOXL4, which promotes the abundant localization of integrin-beta 1 at the cancer plasma membrane. However, it has yet to be uncovered how the LOXL4-mediated abundance of integrin-beta 1 hastens the invasive outgrowth of TNBC cells at the molecular level.
Methods LOXL4-overexpressing stable clones were established from MDA-MB-231 cells and subjected to molecular analyses, real-time qPCR and zymography to clarify their invasiveness, signal transduction, and matrix metalloprotease (MMP) activity, respectively.
Results Our results show that LOXL4 potently promotes the induction of matrix metalloprotease 9 (MMP9) via activation of nuclear factor-kappa B (NF-kappa B). Our molecular analysis revealed that TNF receptor-associated factor 4 (TRAF4) and TGF-beta activated kinase 1 (TAK1) were required for the activation of NF-kappa B through I kappa beta kinase kinase (IKK alpha/beta) phosphorylation.
Conclusion Our results demonstrate that the newly identified LOXL4-mediated axis, integrin-beta 1-TRAF4-TAK1-IKK alpha/beta-I kappa beta alpha-NF-kappa B-MMP9, is crucial for TNBC cell invasiveness.
en-copyright=
kn-copyright=
en-aut-name=JiangFan
en-aut-sei=Jiang
en-aut-mei=Fan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=ChenYouyi
en-aut-sei=Chen
en-aut-mei=Youyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KomalasariNi Luh Gede Yoni
en-aut-sei=Komalasari
en-aut-mei=Ni Luh Gede Yoni
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=Kasano-CamonesCarlos Ichiro
en-aut-sei=Kasano-Camones
en-aut-mei=Carlos Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NinomiyaKazumi
en-aut-sei=Ninomiya
en-aut-mei=Kazumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=YamamotoKen-Ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=GoharaYuma
en-aut-sei=Gohara
en-aut-mei=Yuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=OchiToshiki
en-aut-sei=Ochi
en-aut-mei=Toshiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=RumaI. Made Winarsa
en-aut-sei=Ruma
en-aut-mei=I. Made Winarsa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=SumardikaI. Wayan
en-aut-sei=Sumardika
en-aut-mei=I. Wayan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=ZhouJin
en-aut-sei=Zhou
en-aut-mei=Jin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=HonjoTomoko
en-aut-sei=Honjo
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=SakaguchiYoshihiko
en-aut-sei=Sakaguchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=YamauchiAkira
en-aut-sei=Yamauchi
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=KuribayashiFutoshi
en-aut-sei=Kuribayashi
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=KondoEisaku
en-aut-sei=Kondo
en-aut-mei=Eisaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=InoueYusuke
en-aut-sei=Inoue
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=
en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=
affil-num=1
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine
kn-affil=
affil-num=3
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Faculty of Medicine, Udayana University
kn-affil=
affil-num=6
en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University
kn-affil=
affil-num=7
en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University
kn-affil=
affil-num=8
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Faculty of Medicine, Udayana University
kn-affil=
affil-num=13
en-affil=Faculty of Medicine, Udayana University
kn-affil=
affil-num=14
en-affil=Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology
kn-affil=
affil-num=15
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=16
en-affil=Department of Microbiology, Tokushima Bunri University
kn-affil=
affil-num=17
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=
affil-num=18
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=
affil-num=19
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=20
en-affil=Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University
kn-affil=
affil-num=21
en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University
kn-affil=
affil-num=22
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=23
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=breast cancer
kn-keyword=breast cancer
en-keyword=invasion
kn-keyword=invasion
en-keyword=lysyl oxidase
kn-keyword=lysyl oxidase
en-keyword=NF-κB
kn-keyword=NF-κB
en-keyword=MMP9
kn-keyword=MMP9
END
start-ver=1.4
cd-journal=joma
no-vol=101
cd-vols=
no-issue=4
article-no=
start-page=431
end-page=447
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230304
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Novel extracellular role of REIC/Dkk-3 protein in PD-L1 regulation in cancer cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The adenovirus-REIC/Dkk-3 expression vector (Ad-REIC) has been the focus of numerous clinical studies due to its potential for the quenching of cancers. The cancer-suppressing mechanisms of the REIC/DKK-3 gene depend on multiple pathways that exert both direct and indirect effects on cancers. The direct effect is triggered by REIC/Dkk-3-mediated ER stress that causes cancer-selective apoptosis, and the indirect effect can be classified in two ways: (i) induction, by Ad-REIC-mis-infected cancer-associated fibroblasts, of the production of IL-7, an important activator of T cells and NK cells, and (ii) promotion, by the secretory REIC/Dkk-3 protein, of dendritic cell polarization from monocytes. These unique features allow Ad-REIC to exert effective and selective cancer-preventative effects in the manner of an anticancer vaccine. However, the question of how the REIC/Dkk-3 protein leverages anticancer immunity has remained to be answered. We herein report a novel function of the extracellular REIC/Dkk-3—namely, regulation of an immune checkpoint via modulation of PD-L1 on the cancer-cell surface. First, we identified novel interactions of REIC/Dkk-3 with the membrane proteins C5aR, CXCR2, CXCR6, and CMTM6. These proteins all functioned to stabilize PD-L1 on the cell surface. Due to the dominant expression of CMTM6 among the proteins in cancer cells, we next focused on CMTM6 and observed that REIC/Dkk-3 competed with CMTM6 for PD-L1, thereby liberating PD-L1 from its complexation with CMTM6. The released PD-L1 immediately underwent endocytosis-mediated degradation. These results will enhance our understanding of not only the physiological nature of the extracellular REIC/Dkk-3 protein but also the Ad-REIC-mediated anticancer effects.
en-copyright=
kn-copyright=
en-aut-name=GoharaYuma
en-aut-sei=Gohara
en-aut-mei=Yuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=AudebertLéna
en-aut-sei=Audebert
en-aut-mei=Léna
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=ChenYouyi
en-aut-sei=Chen
en-aut-mei=Youyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KomalasariNi Luh Gede Yoni
en-aut-sei=Komalasari
en-aut-mei=Ni Luh Gede Yoni
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=JiangFan
en-aut-sei=Jiang
en-aut-mei=Fan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=YoshizawaChikako
en-aut-sei=Yoshizawa
en-aut-mei=Chikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=YamamotoKen-ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=WatanabeMasami
en-aut-sei=Watanabe
en-aut-mei=Masami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KumonHiromi
en-aut-sei=Kumon
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=2
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=3
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=4
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=6
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=7
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=8
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=9
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=10
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=11
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=12
en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=13
en-affil=Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University
kn-affil=
affil-num=14
en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
en-keyword=Breast cancer
kn-keyword=Breast cancer
en-keyword=REIC/Dkk-3
kn-keyword=REIC/Dkk-3
en-keyword=PD-L1
kn-keyword=PD-L1
en-keyword=Immune checkpoint
kn-keyword=Immune checkpoint
en-keyword=Cancer therapy
kn-keyword=Cancer therapy
END
start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=
article-no=
start-page=1371342
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240326
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Lysyl oxidase-like 4 promotes the invasiveness of triple-negative breast cancer cells by orchestrating the invasive machinery formed by annexin A2 and S100A11 on the cell surface
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Our earlier research revealed that the secreted lysyl oxidase-like 4 (LOXL4) that is highly elevated in triple-negative breast cancer (TNBC) acts as a catalyst to lock annexin A2 on the cell membrane surface, which accelerates invasive outgrowth of the cancer through the binding of integrin-β1 on the cell surface. However, whether this machinery is subject to the LOXL4-mediated intrusive regulation remains uncertain.
Methods: Cell invasion was assessed using a transwell-based assay, protein–protein interactions by an immunoprecipitation–Western blotting technique and immunocytochemistry, and plasmin activity in the cell membrane by gelatin zymography.
Results: We revealed that cell surface annexin A2 acts as a receptor of plasminogen via interaction with S100A10, a key cell surface annexin A2-binding factor, and S100A11. We found that the cell surface annexin A2/S100A11 complex leads to mature active plasmin from bound plasminogen, which actively stimulates gelatin digestion, followed by increased invasion.
Conclusion: We have refined our understanding of the role of LOXL4 in TNBC cell invasion: namely, LOXL4 mediates the upregulation of annexin A2 at the cell surface, the upregulated annexin 2 binds S100A11 and S100A10, and the resulting annexin A2/S100A11 complex acts as a receptor of plasminogen, readily converting it into active-form plasmin and thereby enhancing invasion.
en-copyright=
kn-copyright=
en-aut-name=TakahashiTetta
en-aut-sei=Takahashi
en-aut-mei=Tetta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=YamamotoKen-Ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KomalasariNi Luh Gede Yoni
en-aut-sei=Komalasari
en-aut-mei=Ni Luh Gede Yoni
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=ChenYouyi
en-aut-sei=Chen
en-aut-mei=Youyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=JiangFan
en-aut-sei=Jiang
en-aut-mei=Fan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=GoharaYuma
en-aut-sei=Gohara
en-aut-mei=Yuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=OchiToshiki
en-aut-sei=Ochi
en-aut-mei=Toshiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=RumaI. Made Winarsa
en-aut-sei=Ruma
en-aut-mei=I. Made Winarsa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=SumardikaI. Wayan
en-aut-sei=Sumardika
en-aut-mei=I. Wayan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=ZhouJin
en-aut-sei=Zhou
en-aut-mei=Jin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=HonjoTomoko
en-aut-sei=Honjo
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=SakaguchiYoshihiko
en-aut-sei=Sakaguchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=YamauchiAkira
en-aut-sei=Yamauchi
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=KuribayashiFutoshi
en-aut-sei=Kuribayashi
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=KondoEisaku
en-aut-sei=Kondo
en-aut-mei=Eisaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=InoueYusuke
en-aut-sei=Inoue
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
en-aut-name=ZamamiYoshito
en-aut-sei=Zamami
en-aut-mei=Yoshito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=
en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=
affil-num=1
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Faculty of Medicine, Udayana University
kn-affil=
affil-num=7
en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine
kn-affil=
affil-num=8
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Faculty of Medicine, Udayana University
kn-affil=
affil-num=12
en-affil=Faculty of Medicine, Udayana University
kn-affil=
affil-num=13
en-affil=Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology
kn-affil=
affil-num=14
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=15
en-affil=Department of Microbiology, Tokushima Bunri University
kn-affil=
affil-num=16
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=
affil-num=17
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=
affil-num=18
en-affil=Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University
kn-affil=
affil-num=19
en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University
kn-affil=
affil-num=20
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=21
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=22
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=
affil-num=23
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=breast cancer
kn-keyword=breast cancer
en-keyword=lysyl oxidase
kn-keyword=lysyl oxidase
en-keyword=annexin A2
kn-keyword=annexin A2
en-keyword=S100A11
kn-keyword=S100A11
en-keyword=plasmin
kn-keyword=plasmin
en-keyword=cancer microenvironment
kn-keyword=cancer microenvironment
END
start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=19
article-no=
start-page=11035
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220920
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-gamma production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-gamma expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103(+)CD11b(+) dendritic cells (DCs) into the mLN, along with increased (1 -> 3)-beta-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103(+)CD11b(+) DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development.
en-copyright=
kn-copyright=
en-aut-name=ShigehiroTsukasa
en-aut-sei=Shigehiro
en-aut-mei=Tsukasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=UenoMaho
en-aut-sei=Ueno
en-aut-mei=Maho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KijihiraMayumi
en-aut-sei=Kijihira
en-aut-mei=Mayumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TakahashiRyotaro
en-aut-sei=Takahashi
en-aut-mei=Ryotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=UmemuraChiho
en-aut-sei=Umemura
en-aut-mei=Chiho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TahaEman A.
en-aut-sei=Taha
en-aut-mei=Eman A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KurosakaChisaki
en-aut-sei=Kurosaka
en-aut-mei=Chisaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=AsayamaMegumi
en-aut-sei=Asayama
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=MurakamiHiroshi
en-aut-sei=Murakami
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=SatohAyano
en-aut-sei=Satoh
en-aut-mei=Ayano
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=NakamuraYoshimasa
en-aut-sei=Nakamura
en-aut-mei=Yoshimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=MasudaJunko
en-aut-sei=Masuda
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
affil-num=1
en-affil=Research Institute for Biomedical Sciences, Tokyo University of Science
kn-affil=
affil-num=2
en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University
kn-affil=
affil-num=4
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=5
en-affil=Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
affil-num=6
en-affil=Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University
kn-affil=
affil-num=9
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=10
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=11
en-affil=Graduate School of Environmental and Life Science, Okayama University
kn-affil=
affil-num=12
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=13
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=breast cancer cells
kn-keyword=breast cancer cells
en-keyword=dendritic cells
kn-keyword=dendritic cells
en-keyword=mesenteric lymph node
kn-keyword=mesenteric lymph node
en-keyword=myeloid-derived suppressor cells
kn-keyword=myeloid-derived suppressor cells
END
start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=18
article-no=
start-page=10300
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220907
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Histidine-Rich Glycoprotein Suppresses the S100A8/A9-Mediated Organotropic Metastasis of Melanoma Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The dissection of the complex multistep process of metastasis exposes vulnerabilities that could be exploited to prevent metastasis. To search for possible factors that favor metastatic outgrowth, we have been focusing on secretory S100A8/A9. A heterodimer complex of the S100A8 and S100A9 proteins, S100A8/A9 functions as a strong chemoattractant, growth factor, and immune suppressor, both promoting the cancer milieu at the cancer-onset site and cultivating remote, premetastatic cancer sites. We previously reported that melanoma cells show lung-tropic metastasis owing to the abundant expression of S100A8/A9 in the lung. In the present study, we addressed the question of why melanoma cells are not metastasized into the brain at significant levels in mice despite the marked induction of S100A8/A9 in the brain. We discovered the presence of plasma histidine-rich glycoprotein (HRG), a brain-metastasis suppression factor against S100A8/A9. Using S100A8/A9 as an affinity ligand, we searched for and purified the binding plasma proteins of S100A8/A9 and identified HRG as the major protein on mass spectrometric analysis. HRG prevents the binding of S100A8/A9 to the B16-BL6 melanoma cell surface via the formation of the S100A8/A9 complex. HRG also inhibited the S100A8/A9-induced migration and invasion of A375 melanoma cells. When we knocked down HRG in mice bearing skin melanoma, metastasis to both the brain and lungs was significantly enhanced. The clinical examination of plasma S100A8/A9 and HRG levels showed that lung cancer patients with brain metastasis had higher S100A8/A9 and lower HRG levels than nonmetastatic patients. These results suggest that the plasma protein HRG strongly protects the brain and lungs from the threat of melanoma metastasis.
en-copyright=
kn-copyright=
en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=WakeHidenori
en-aut-sei=Wake
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=InoueYusuke
en-aut-sei=Inoue
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=RumaI. Made Winarsa
en-aut-sei=Ruma
en-aut-mei=I. Made Winarsa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=GoharaYuma
en-aut-sei=Gohara
en-aut-mei=Yuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KomalasariNi Luh Gede Yoni
en-aut-sei=Komalasari
en-aut-mei=Ni Luh Gede Yoni
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=JiangFan
en-aut-sei=Jiang
en-aut-mei=Fan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=YamamotoKen-Ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=SumardikaI. Wayan
en-aut-sei=Sumardika
en-aut-mei=I. Wayan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=ChenYouyi
en-aut-sei=Chen
en-aut-mei=Youyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=YamauchiAkira
en-aut-sei=Yamauchi
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=KuribayashiFutoshi
en-aut-sei=Kuribayashi
en-aut-mei=Futoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=KondoEisaku
en-aut-sei=Kondo
en-aut-mei=Eisaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=NishiboriMasahiro
en-aut-sei=Nishibori
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
affil-num=1
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Pharmacology, Kindai University Faculty of Medicine
kn-affil=
affil-num=4
en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University
kn-affil=
affil-num=5
en-affil=Faculty of Medicine, Udayana University
kn-affil=
affil-num=6
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Faculty of Medicine, Udayana University
kn-affil=
affil-num=13
en-affil=Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University
kn-affil=
affil-num=14
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=15
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=
affil-num=16
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=
affil-num=17
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=
affil-num=18
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=19
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=20
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=S100A8/A9
kn-keyword=S100A8/A9
en-keyword=HRG
kn-keyword=HRG
en-keyword=metastasis
kn-keyword=metastasis
END
start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=
article-no=
start-page=869393
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220504
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Engineering Cancer/Testis Antigens With Reversible S-Cationization to Evaluate Antigen Spreading
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Serum autoantibody to cancer/testis antigens (CTAs) is a critical biomarker that reflects the antitumor immune response. Quantitative and multiplexed anti-CTA detection arrays can assess the immune status in tumors and monitor therapy-induced antitumor immune reactions. Most full-length recombinant CTA proteins tend to aggregate. Cysteine residue-specific S-cationization techniques facilitate the preparation of water-soluble and full-length CTAs. Combined with Luminex technology, we designed a multiple S-cationized antigen-immobilized bead array (MUSCAT) assay system to evaluate multiple serum antibodies to CTAs. Reducible S-alkyl-disulfide-cationized antigens in cytosolic conditions were employed to develop rabbit polyclonal antibodies as positive controls. These control antibodies sensitively detected immobilized antigens on beads and endogenous antigens in human lung cancer-derived cell lines. Rabbit polyclonal antibodies successfully confirmed the dynamic ranges and quantitative MUSCAT assay results. An immune monitoring study was conducted using the serum samples on an adenovirus-mediated REIC/Dkk-3 gene therapy clinical trial that showed a successful clinical response in metastatic castration-resistant prostate cancer. Autoantibody responses were closely related to clinical outcomes. Notably, upregulation of anti-CTA responses was monitored before tumor regression. Thus, quantitative monitoring of anti-CTA antibody biomarkers can be used to evaluate the cancer-immunity cycle. A quality-certified serum autoantibody monitoring system is a powerful tool for developing and evaluating cancer immunotherapy.
en-copyright=
kn-copyright=
en-aut-name=MiyamotoAi
en-aut-sei=Miyamoto
en-aut-mei=Ai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=HonjoTomoko
en-aut-sei=Honjo
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MasuiMirei
en-aut-sei=Masui
en-aut-mei=Mirei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KumonHiromi
en-aut-sei=Kumon
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KakimiKazuhiro
en-aut-sei=Kakimi
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
affil-num=1
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Innovation Center Okayama for Nanobio-targeted Therapy, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Immunotherapeutics, The University of Tokyo Hospital
kn-affil=
affil-num=7
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=autoantibody
kn-keyword=autoantibody
en-keyword=biomarker
kn-keyword=biomarker
en-keyword=protein engineering
kn-keyword=protein engineering
en-keyword=cancer-immunity cycle
kn-keyword=cancer-immunity cycle
en-keyword=immune monitoring
kn-keyword=immune monitoring
en-keyword=cancer
kn-keyword=cancer
en-keyword=testis antigens
kn-keyword=testis antigens
END
start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=2
article-no=
start-page=285
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220131
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The role of Dickkopf-3 (Dkk3)/REIC (The Reduced Expression in Immortalized Cells), a Wnt-signaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of Dkk3/REIC in the male reproductive process, we studied the Dkk3/REIC knock-out (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between Dkk3/REIC-KO and wild-type (WT) male mice. To further explore the underlying molecular mechanism, we performed RNA sequencing (RNA-seq) analysis of testicular tissues. Our results showed that spermiation failure existed in seminiferous tubules of Dkk3/REIC-KO mice, and sperm from Dkk3/REIC-KO mice exhibited inferior motility (44.09 +/- 8.12% vs. 23.26 +/- 10.02%, p < 0.01). The Ultrastructure examination revealed defects in the sperm fibrous sheath of KO mice. Although the average count of Dkk3/REIC-KO epididymal sperm was less than that of the wild-types (9.30 +/- 0.69 vs. 8.27 +/- 0.87, x10(6)), neither the gap (p > 0.05) nor the difference in the sperm vitality rate (72.83 +/- 1.55% vs. 72.50 +/- 0.71%, p > 0.05) were statistically significant. The RNA-seq and GO (Gene Oncology) enrichment results indicated that the differential genes were significantly enriched in the GO terms of cytoskeleton function, cAMP signaling and calcium ion binding. Collectively, our research demonstrates that Dkk3/REIC is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice.
en-copyright=
kn-copyright=
en-aut-name=XueRuizhi
en-aut-sei=Xue
en-aut-mei=Ruizhi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=LinWenfeng
en-aut-sei=Lin
en-aut-mei=Wenfeng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=FujitaHirofumi
en-aut-sei=Fujita
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=SunJingkai
en-aut-sei=Sun
en-aut-mei=Jingkai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=OchiaiKazuhiko
en-aut-sei=Ochiai
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=WatanabeMasami
en-aut-sei=Watanabe
en-aut-mei=Masami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=OhuchiHideyo
en-aut-sei=Ohuchi
en-aut-mei=Hideyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=TangZhengyan
en-aut-sei=Tang
en-aut-mei=Zhengyan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=HuangPeng
en-aut-sei=Huang
en-aut-mei=Peng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=NasuYasutomo
en-aut-sei=Nasu
en-aut-mei=Yasutomo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KumonHiromi
en-aut-sei=Kumon
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Laboratory of Veterinary Hygiene, Nippon Veterinary and Life Science University
kn-affil=
affil-num=7
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Urology, Xiangya Hospital, Central South University
kn-affil=
affil-num=12
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University
kn-affil=
en-keyword=Dkk3/REIC
kn-keyword=Dkk3/REIC
en-keyword=fibrous sheath
kn-keyword=fibrous sheath
en-keyword=knock-out
kn-keyword=knock-out
en-keyword=RNA-seq
kn-keyword=RNA-seq
en-keyword=spermiation
kn-keyword=spermiation
en-keyword=sperm motility
kn-keyword=sperm motility
END
start-ver=1.4
cd-journal=joma
no-vol=170
cd-vols=
no-issue=3
article-no=
start-page=435
end-page=443
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=2021710
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Unusual aggregation property of recombinantly expressed cancer-testis antigens in mammalian cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Transient expression of human intracellular proteins in human embryonic kidney (HEK) 293 cells is a reliable system for obtaining soluble proteins with biologically active conformations. Contrary to conventional concepts, we found that recombinantly expressed intracellular cancer-testis antigens (CTAs) showed frequent aggregation in HEK293 cells. Although experimental subcellular localization of recombinant CTAs displayed proper cytosolic or nuclear localization, some proteins showed aggregated particles in the cell. This aggregative property was not observed in recombinant housekeeping proteins. No significant correlation was found between the aggregative and biophysical properties, such as hydrophobicity, contents of intrinsically disordered regions and expression levels, of CTAs. These results can be explained in terms of structural instability of CTAs, which are specifically expressed in the testis and aberrantly expressed in cancer cells and function as a hub in the protein–protein network using intrinsically disordered regions. Hence, we speculate that recombinantly expressed CTAs failed to form this protein complex. Thus, unfolded CTAs formed aggregated particles in the cell.
en-copyright=
kn-copyright=
en-aut-name=AhmadiHannaneh
en-aut-sei=Ahmadi
en-aut-mei=Hannaneh
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=ShogenKohei
en-aut-sei=Shogen
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=FujitaKana
en-aut-sei=Fujita
en-aut-mei=Kana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=HonjoTomoko
en-aut-sei=Honjo
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KakimiKazuhiro
en-aut-sei=Kakimi
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
affil-num=1
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Immunotherapeutics, The University of Tokyo Hospital
kn-affil=
affil-num=6
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=12
article-no=
start-page=2071
end-page=2083
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20191231
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction: Programmed cell death-1 (PD-1) inhibitors effectively treat NSCLC and prolong survival. Robust biomarkers for predicting clinical benefits of good response and long survival with anti-PD-1 therapy have yet to be identified; therefore, predictive biomarkers are needed to select patients with benefits.
Methods: We conducted a prospective study to explore whether serum antibody against NY-ESO-1 and/or XAGE1 cancer-testis antigens predicted primarily good clinical response and secondarily long survival with anti-PD-1 therapy for NSCLC. The serum antibody was detected by enzyme-linked immunosorbent assay, and tumor immune microenvironment and mutation burden were analyzed by immunohistochemistry and next-generation sequencing.
Results: In the discovery cohort (n = 13), six antibody-positive NSCLC cases responded to anti-PD-1 therapy (two complete and four partial responses), whereas seven antibody-negative NSCLC cases did not. Antibody positivity was associated with good response and survival, regardless of tumor programmed death ligand 1 (PD-L1) expression, mutation burden, and CD8+ T-cell infiltration. In the validation cohort (n = 75), 17 antibody-positive NSCLC cases responded well to anti-PD-1 therapy as compared with 58 negative NSCLC cases (objective response rate 65% versus 19%, p = 0.0006) and showed significantly prolonged progression-free survival and overall survival. Antibody titers highly correlated with tumor reduction rates. In the multivariate analysis, response biomarkers were tumor programmed death ligand 1 expression and antibody positivity, and only antibody positivity was a significantly better predictive biomarker of progression-free survival (hazard ratio = 0.4, p = 0.01) and overall survival (hazard ratio = 0.2, p = 0.004).
Conclusions: Our results suggest that NY-ESO-1 and/or XAGE1 serum antibodies are useful biomarkers for predicting clinical benefits in anti-PD-1 therapy for NSCLC and probably for other cancers.
en-copyright=
kn-copyright=
en-aut-name=OhueYoshihiro
en-aut-sei=Ohue
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KuroseKoji
en-aut-sei=Kurose
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KarasakiTakahiro
en-aut-sei=Karasaki
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=IsobeMidori
en-aut-sei=Isobe
en-aut-mei=Midori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=YamaokaTakaaki
en-aut-sei=Yamaoka
en-aut-mei=Takaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=IreiIsao
en-aut-sei=Irei
en-aut-mei=Isao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=MasudaTakeshi
en-aut-sei=Masuda
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=FukudaMasaaki
en-aut-sei=Fukuda
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KinoshitaAkitoshi
en-aut-sei=Kinoshita
en-aut-mei=Akitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=MatsushitaHirokazu
en-aut-sei=Matsushita
en-aut-mei=Hirokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=ShimizuKatsuhiko
en-aut-sei=Shimizu
en-aut-mei=Katsuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=NakataMasao
en-aut-sei=Nakata
en-aut-mei=Masao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=HattoriNoboru
en-aut-sei=Hattori
en-aut-mei=Noboru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=YamaguchiHiroyuki
en-aut-sei=Yamaguchi
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=FukudaMinoru
en-aut-sei=Fukuda
en-aut-mei=Minoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=NozawaRyohei
en-aut-sei=Nozawa
en-aut-mei=Ryohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=KakimiKazuhiro
en-aut-sei=Kakimi
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=OkaMikio
en-aut-sei=Oka
en-aut-mei=Mikio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
affil-num=1
en-affil=Department of Respiratory Medicine, Kawasaki Medical School
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Kawasaki Medical School
kn-affil=
affil-num=3
en-affil=Department of Thoracic Surgery, The University of Tokyo
kn-affil=
affil-num=4
en-affil=Department of Respiratory Medicine, Kawasaki Medical School
kn-affil=
affil-num=5
en-affil=Department of Respiratory Medicine, Kawasaki Medical School
kn-affil=
affil-num=6
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Pathology, Kawasaki Medical School
kn-affil=
affil-num=8
en-affil=Department of Respiratory Internal Medicine, Hiroshima University Hospital
kn-affil=
affil-num=9
en-affil=Department of Respiratory Medicine, The Japanese Red Cross Nagasaki Genbaku Hospital
kn-affil=
affil-num=10
en-affil=Department of Respiratory Medicine, Nagasaki Prefecture Shimabara Hospital
kn-affil=
affil-num=11
en-affil=Department of Immunotherapeutics, Graduate School of Medicine, The University of Tokyo
kn-affil=
affil-num=12
en-affil=Department of General Thoracic Surgery, Kawasaki Medical School
kn-affil=
affil-num=13
en-affil=Department of General Thoracic Surgery, Kawasaki Medical School
kn-affil=
affil-num=14
en-affil=Department of Respiratory Internal Medicine, Hiroshima University Hospital
kn-affil=
affil-num=15
en-affil=Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences
kn-affil=
affil-num=16
en-affil=Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences
kn-affil=
affil-num=17
en-affil=Faculty of Health and Welfare Services Administration, Kawasaki University of Medical Welfare
kn-affil=
affil-num=18
en-affil=Department of Immunotherapeutics, Graduate School of Medicine, The University of Tokyo
kn-affil=
affil-num=19
en-affil=Department of Immuno-Oncology, Kawasaki Medical School
kn-affil=
en-keyword=Biomarker
kn-keyword=Biomarker
en-keyword=Anti-programmed death 1 therapy
kn-keyword=Anti-programmed death 1 therapy
en-keyword=NSCLC
kn-keyword=NSCLC
en-keyword=Cancer-testis antigen
kn-keyword=Cancer-testis antigen
en-keyword=Serum antibody
kn-keyword=Serum antibody
END
start-ver=1.4
cd-journal=joma
no-vol=21
cd-vols=
no-issue=7
article-no=
start-page=627
end-page=640
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=201907
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Metastatic breast cancer is the leading cause of cancer-associated death in women. The progression of this fatal disease is associated with inflammatory responses that promote cancer cell growth and dissemination, eventually leading to a reduction of overall survival. However, the mechanism(s) of the inflammation-boosted cancer progression remains unclear. In this study, we found for the first time that an extracellular cytokine, S100A8/A9, accelerates breast cancer growth and metastasis upon binding to a cell surface receptor, melanoma cell adhesion molecule (MCAM). Our molecular analyses revealed an important role of ETS translocation variant 4 (ETV4), which is significantly activated in the region downstream of MCAM upon S100A8/A9 stimulation, in breast cancer progression in vitro as well as in vivo. The MCAM-mediated activation of ETV4 induced a mobile phenotype called epithelial-mesenchymal transition (EMT) in cells, since we found that ETV4 transcriptionally upregulates ZEB1, a strong EMT inducer, at a very high level. In contrast, downregulation of either MCAM or ETV4 repressed EMT, resulting in greatly weakened tumor growth and lung metastasis. Overall, our results revealed that ETV4 is a novel transcription factor regulated by the S100A8/A9-MCAM axis, which leads to EMT through ZEB1 and thereby to metastasis in breast cancer cells. Thus, therapeutic strategies based on our findings might improve patient outcomes.
en-copyright=
kn-copyright=
en-aut-name=ChenYouyi
en-aut-sei=Chen
en-aut-mei=Youyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=SumardikaI Wayan
en-aut-sei=Sumardika
en-aut-mei=I Wayan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=InoueYusuke
en-aut-sei=Inoue
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=IiokaHidekazu
en-aut-sei=Iioka
en-aut-mei=Hidekazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MitsuiYosuke
en-aut-sei=Mitsui
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=SaitoKen
en-aut-sei=Saito
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=RumaI Made Winarsa
en-aut-sei=Ruma
en-aut-mei=I Made Winarsa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=SatoHiroki
en-aut-sei=Sato
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=YamauchiAkira
en-aut-sei=Yamauchi
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=YamamotoKen-ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=SohJunichi
en-aut-sei=Soh
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=KuboMiyoko
en-aut-sei=Kubo
en-aut-mei=Miyoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=PutrantoEndy Widya
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en-aut-mei=Endy Widya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=MurakamiTakashi
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kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
en-aut-name=LiuMing
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kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=
en-aut-name=HibinoToshihiko
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kn-aut-sei=
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aut-affil-num=23
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en-aut-name=NishiboriMasahiro
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en-aut-name=KondoEisaku
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en-aut-name=ToyookaShinichi
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en-aut-name=SakaguchiMasakiyo
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kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=27
ORCID=
affil-num=1
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University
kn-affil=
affil-num=6
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=
affil-num=7
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=
affil-num=9
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Biochemistry, Kawasaki Medical School
kn-affil=
affil-num=12
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Biobank, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=17
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=18
en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
affil-num=19
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=20
en-affil=Department of Pediatrics, Dr. Sardjito Hospital/Faculty of Medicine, Universitas Gadjah Mada
kn-affil=
affil-num=21
en-affil=Department of Microbiology, Faculty of Medicine, Saitama Medical University
kn-affil=
affil-num=22
en-affil=Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University
kn-affil=
affil-num=23
en-affil=Department of Dermatology, Tokyo Medical University
kn-affil=
affil-num=24
en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=25
en-affil=Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
kn-affil=
affil-num=26
en-affil=Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=27
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=33
cd-vols=
no-issue=5
article-no=
start-page=19
end-page=24
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=20160512
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Development of Antibody Detection System to Evaluate Activation of Anti-Tumor Immune Respons
kn-title=腫瘍免疫応答の活性化を測定する抗体検査技術の開発
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=がん免疫治療や関連の医薬品開発において、腫瘍に対する免疫応答のレベルを簡便な血液検査で定量評価ができる診断技術が必要だ。がんに対する免疫応答が亢進している際には、血液中に様々な抗がん抗原抗体が増加する。この抗体価の定量評価には、独自開発の変性タンパク質の可溶化技術の活用が強力な手段となる。
en-copyright=
kn-copyright=
en-aut-name=FutamiJunichiro
en-aut-sei=Futami
en-aut-mei=Junichiro
kn-aut-name=二見淳一郎
kn-aut-sei=二見
kn-aut-mei=淳一郎
aut-affil-num=1
ORCID=
affil-num=1
en-affil=
kn-affil=岡山大学大学院自然科学研究科
END
start-ver=1.4
cd-journal=joma
no-vol=32
cd-vols=
no-issue=4
article-no=
start-page=938
end-page=944
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201310
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Inhibition of RAGE signaling through the intracellular delivery of inhibitor peptides by PEI cationization
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The receptor for advanced glycation end products (RAGE) is a multi-ligand cell surface receptor and a member of the immunoglobulin superfamily. RAGE is involved in a wide range of inflammatory, degenerative and hyper-proliferative disorders which span over different organs by engaging diverse ligands, including advanced glycation end products, S100 family proteins, high-mobility group protein B1 (HMGB1) and amyloid beta. We previously demonstrated that the cytoplasmic domain of RAGE is phosphorylated upon the binding of ligands, enabling the recruitment of two distinct pairs of adaptor proteins, Toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP) and myeloid differentiation protein 88 (MyD88). This engagement allows the activation of downstream effector molecules, and thereby mediates a wide variety of cellular processes, such as inflammatory responses, apoptotic cell death, migration and cell growth. Therefore, inhibition of the binding of TIRAP to RAGE may abrogate intracellular signaling from ligand-activated RAGE. In the present study, we developed inhibitor peptides for RAGE signaling (RAGE-I) by mimicking the phosphorylatable cytosolic domain of RAGE. RAGE-I was efficiently delivered into the cells by polyethylenimine (PEI) cationization. We demonstrated that RAGE-I specifically bound to TIRAP and abrogated the activation of Cdc42 induced by ligand-activated RAGE. Furthermore, we were able to reduce neuronal cell death induced by an excess amount of S100B and to inhibit the migration and invasion of glioma cells in vitro. Our results indicate that RAGE-I provides a powerful tool for therapeutics to block RAGE-mediated multiple signaling.
en-copyright=
kn-copyright=
en-aut-name=PutrantoEndy Widya
en-aut-sei=Putranto
en-aut-mei=Endy Widya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=MurataHitoshi
en-aut-sei=Murata
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=YamamotoKen-Ichi
en-aut-sei=Yamamoto
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KataokaKen
en-aut-sei=Kataoka
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=YamadaHidenori
en-aut-sei=Yamada
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=FutamiJun-Ichiro
en-aut-sei=Futami
en-aut-mei=Jun-Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=HuhNam-Ho
en-aut-sei=Huh
en-aut-mei=Nam-Ho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol
affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol
affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol
affil-num=4
en-affil=
kn-affil=Okayama Univ Sci, Fac Sci, Dept Life Sci
affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Nat Sci & Biotechnol, Dept Med Bioengn Sci
affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Nat Sci & Biotechnol, Dept Med Bioengn Sci
affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol
affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol
en-keyword=receptor for advanced glycation end products
kn-keyword=receptor for advanced glycation end products
en-keyword=Toll-interleukin 1 receptor domain-containing adaptor protein
kn-keyword=Toll-interleukin 1 receptor domain-containing adaptor protein
en-keyword=cationization
kn-keyword=cationization
en-keyword=S100B
kn-keyword=S100B
en-keyword=cell death
kn-keyword=cell death
en-keyword=cell migration
kn-keyword=cell migration
END
start-ver=1.4
cd-journal=joma
no-vol=118
cd-vols=
no-issue=3
article-no=
start-page=215
end-page=220
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2007
dt-pub=20070104
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=内臓脂肪組織に由来するセリンプロテアーゼ阻害剤：Vaspin の同定肥満状態でインスリン感受性を高める新規アディポサイトカイン
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=肥田和之
kn-aut-sei=肥田
kn-aut-mei=和之
aut-affil-num=1
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=和田淳
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aut-affil-num=2
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=江口潤
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kn-aut-mei=潤
aut-affil-num=3
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=ZhangHong
kn-aut-sei=Zhang
kn-aut-mei=Hong
aut-affil-num=4
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=馬場雅子
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kn-aut-mei=雅子
aut-affil-num=5
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=清田綾
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kn-aut-mei=綾
aut-affil-num=6
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=橋本泉
kn-aut-sei=橋本
kn-aut-mei=泉
aut-affil-num=7
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=岡田達夫
kn-aut-sei=岡田
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aut-affil-num=8
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=安原章浩
kn-aut-sei=安原
kn-aut-mei=章浩
aut-affil-num=9
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=中司敦子
kn-aut-sei=中司
kn-aut-mei=敦子
aut-affil-num=10
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=赤木滋
kn-aut-sei=赤木
kn-aut-mei=滋
aut-affil-num=11
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=四方賢一
kn-aut-sei=四方
kn-aut-mei=賢一
aut-affil-num=12
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=宝来真志
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kn-aut-mei=真志
aut-affil-num=13
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=二見淳一郎
kn-aut-sei=二見
kn-aut-mei=淳一郎
aut-affil-num=14
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=渡辺英二郎
kn-aut-sei=渡辺
kn-aut-mei=英二郎
aut-affil-num=15
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=松木泰
kn-aut-sei=松木
kn-aut-mei=泰
aut-affil-num=16
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=平松隆司
kn-aut-sei=平松
kn-aut-mei=隆司
aut-affil-num=17
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=槇野博史
kn-aut-sei=槇野
kn-aut-mei=博史
aut-affil-num=18
ORCID=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=Yashpal S.Kanwar
kn-aut-sei=Yashpal S.
kn-aut-mei=Kanwar
aut-affil-num=19
ORCID=
affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学
affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学
affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学
affil-num=4
en-affil=
kn-affil=北京大学第一医院腎臓研究所
affil-num=5
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学
affil-num=6
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学
affil-num=7
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学
affil-num=8
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学
affil-num=9
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学
affil-num=10
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学
affil-num=11
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学
affil-num=12
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学
affil-num=13
en-affil=
kn-affil=住友化学工業㈱生物環境科学研究所
affil-num=14
en-affil=
kn-affil=岡山大学工学部 生物機能工学科蛋白質機能工学研究室
affil-num=15
en-affil=
kn-affil=大日本住友製薬㈱大阪研究所宝塚分室ゲノム研究所
affil-num=16
en-affil=
kn-affil=大日本住友製薬㈱大阪研究所宝塚分室ゲノム研究所
affil-num=17
en-affil=
kn-affil=大日本住友製薬㈱大阪研究所宝塚分室ゲノム研究所
affil-num=18
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学
affil-num=19
en-affil=
kn-affil=ノースウェスタン大学病理学教室
en-keyword=Vaspin
kn-keyword=Vaspin
en-keyword=アディポサイトカイン
kn-keyword=アディポサイトカイン
en-keyword=内臓脂肪
kn-keyword=内臓脂肪
en-keyword=インスリン抵抗性
kn-keyword=インスリン抵抗性
en-keyword=メタボリックシンドローム
kn-keyword=メタボリックシンドローム
END
start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=1999
dt-pub=19990325
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=ヒト膵由来型リボヌクレアーゼに関する研究とヒト化したイムノトキシンの開発への応用
kn-title=Study on Human Pancreatic-field name="type" Ribonucleases and Application to the Development of Humanized Immunotoxin
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=二見淳一郎
kn-aut-sei=二見
kn-aut-mei=淳一郎
aut-affil-num=1
ORCID=
affil-num=1
en-affil=
kn-affil=岡山大学
END