start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=1
article-no=
start-page=13
end-page=24
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=201602
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Function of β2-glycoprotein I in Angiogenesis and Its in Vivo Distribution in Tumor Xenografts
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Intact β2-glycoprotein I (iβ2GPI) is a glycoprotein that regulates coagulation and fibrinolysis. Nicked β2GPI (nβ2GPI) possesses an angiogenic property at a relatively low concentration, and an antiangiogenic property at a high concentration. Here we investigated the functions of βi 2GPI and nβ2GPI in vascular endothelial growth factor (VEGF)-A-induced endothelial cell proliferation and tube formation. We used noninvasive PET imaging to analyze the in vivo distribution of intravenously injected β2GPI variants in tumor lesions in mice. iβ2GPI was incubated with plasmin to obtain nβ2GPI, and its N-terminal sequence was analyzed. nβ2GPI had at least one other cleavage site upstream of the β2GPIʼs domain V, whereas the former plasmin-cleavage site locates between K317 and T318. Both of intact and nicked β2GPI significantly inhibited the VEGF-A-induced cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs). PET imaging visualized considerably distributed intensities of all tested β2GPI variants in tumor lesions of pancreatic tumor cell-xenografts. These results indicate that β2GPI may be physiologically and pathophysiologically important in the regulation of not only coagulation and fibrinolysis, but also angiogenesis.
en-copyright=
kn-copyright=

en-aut-name=Arum Tri Wahyuningsih
en-aut-sei=Arum Tri Wahyuningsih
en-aut-mei=
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShenLianhua
en-aut-sei=Shen
en-aut-mei=Lianhua
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KobayashiKazuko
en-aut-sei=Kobayashi
en-aut-mei=Kazuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SasakiTakanori
en-aut-sei=Sasaki
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakenakaFumiaki
en-aut-sei=Takenaka
en-aut-mei=Fumiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HanadaTakahisa
en-aut-sei=Hanada
en-aut-mei=Takahisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=AkehiMasaru
en-aut-sei=Akehi
en-aut-mei=Masaru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AkahoshiAkiya
en-aut-sei=Akahoshi
en-aut-mei=Akiya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OzekiEiichi
en-aut-sei=Ozeki
en-aut-mei=Eiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=AndoEiji
en-aut-sei=Ando
en-aut-mei=Eiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=MatsuuraEiji
en-aut-sei=Matsuura
en-aut-mei=Eiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Cell Chemistry , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=3
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=6
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=7
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=8
en-affil=
kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=9
en-affil=
kn-affil=Technology Research Laboratory, Shimadzu Corporation

affil-num=10
en-affil=
kn-affil=Life Science Business Department, Shimadzu Corporation

affil-num=11
en-affil=
kn-affil=Department of Cell Chemistry , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=β2-glycoprotein I (β2GPI)
kn-keyword=β2-glycoprotein I (β2GPI)
en-keyword=angiogenesis
kn-keyword=angiogenesis
en-keyword=vascular endothelial growth factor-A (VEGF-A)
kn-keyword=vascular endothelial growth factor-A (VEGF-A)
en-keyword=positron emission tomography (PET) imaging
kn-keyword=positron emission tomography (PET) imaging
END