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 ƒÀ2-glycoprotein I in Angiogenesis and Its in Vivo Distribution in Tumor Xenografts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intact ƒÀ2-glycoprotein I (iƒÀ2GPI) is a glycoprotein that regulates coagulation and fibrinolysis. Nicked ƒÀ2GPI (nƒÀ2GPI) possesses an angiogenic property at a relatively low concentration, and an antiangiogenic property at a high concentration. Here we investigated the functions of ƒÀi 2GPI and nƒÀ2GPI 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 ƒÀ2GPI variants in tumor lesions in mice. iƒÀ2GPI was incubated with plasmin to obtain nƒÀ2GPI, and its N-terminal sequence was analyzed. nƒÀ2GPI had at least one other cleavage site upstream of the ƒÀ2GPI?s domain V, whereas the former plasmin-cleavage site locates between K317 and T318. Both of intact and nicked ƒÀ2GPI 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 ƒÀ2GPI variants in tumor lesions of pancreatic tumor cell-xenografts. These results indicate that ƒÀ2GPI 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=ƒÀ2-glycoprotein I (ƒÀ2GPI) kn-keyword=ƒÀ2-glycoprotein I (ƒÀ2GPI) 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