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ID 61398
フルテキストURL
著者
Ono, Kisho Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaken ID researchmap
Sogawa, Chiharu Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kawai, Hotaka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Manh Tien Tran Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Taha, Eman A. Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Lu, Yanyin Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
May Wathone Oo Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Okusha, Yuka Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaken ID researchmap
Okamura, Hirohiko Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University ORCID Kaken ID publons researchmap
Ibaragi, Soichiro Department of Oral and Maxillofacial Surgery, Okayama University Hospital ORCID Kaken ID publons researchmap
Takigawa, Masaharu Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaken ID publons researchmap
Kozaki, Ken-Ichi Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nagatsuka, Hitoshi Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kaken ID publons researchmap
Sasaki, Akira Department of Oral and Maxillofacial Surgery, Okayama University Hospital Kaken ID publons researchmap
Okamoto, Kuniaki Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaken ID researchmap
Calderwood, Stuart K. Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School
Eguchi, Takanori Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University ORCID Kaken ID publons researchmap
抄録
Evidence has been accumulating to indicate that extracellular vesicles (EVs), including exosomes, released by cancer cells can foster tumour progression. The molecular chaperones – CDC37, HSP90α and HSP90β play key roles in cancer progression including epithelial‐mesenchymal transition (EMT), although their contribution to EVs‐mediated cell–cell communication in tumour microenvironment has not been thoroughly examined. Here we show that triple depletion of the chaperone trio attenuates numerous cancer malignancy events exerted through EV release. Metastatic oral cancer‐derived EVs (MEV) were enriched with HSP90α HSP90β and cancer‐initiating cell marker CD326/EpCAM. Depletion of these chaperones individually induced compensatory increases in the other chaperones, whereas triple siRNA targeting of these molecules markedly diminished the levels of the chaperone trio and attenuated EMT. MEV were potent agents in initiating EMT in normal epithelial cells, a process that was attenuated by the triple chaperone depletion. The migration, invasion, and in vitro tumour initiation of oral cancer cells were significantly promoted by MEV, while triple depletion of CDC37/HSP90α/β reversed these MEV‐driven malignancy events. In metastatic oral cancer patient‐derived tumours, HSP90β was significantly accumulated in infiltrating tumour‐associated macrophages (TAM) as compared to lower grade oral cancer cases. HSP90‐enriched MEV‐induced TAM polarization to an M2 phenotype, a transition known to support cancer progression, whereas the triple chaperone depletion attenuated this effect. Mechanistically, the triple chaperone depletion in metastatic oral cancer cells effectively reduced MEV transmission into macrophages. Hence, siRNA‐mediated knockdown of the chaperone trio (CDC37/HSP90α/HSP90β) could potentially be a novel therapeutic strategy to attenuate several EV‐driven malignancy events in the tumour microenvironment.
キーワード
Extracellular vesicles
epithelial‐mesenchymal transition
tumour‐associated macrophage
CDC37
HSP90
tetraspanin
oral cancer
発行日
2020-05-31
出版物タイトル
Journal of Extracellular Vesicles
9巻
1号
出版者
Taylor & Francis
開始ページ
1769373
ISSN
2001-3078
資料タイプ
学術雑誌論文
言語
英語
OAI-PMH Set
岡山大学
著作権者
© 2020 The Author(s).
論文のバージョン
publisher
PubMed ID
DOI
関連URL
isVersionOf https://doi.org/10.1080/20013078.2020.1769373
ライセンス
http://creativecommons.org/licenses/by‐nc/4.0/
助成機関名
日本学術振興会
助成番号
17K11642
17K11643
17K11669
19K24072
16K11722-JM
19K10288-JM
18K09789-KN
JP16K11441
JP20H03888
19H03817
19H04051
20K09904