title: The Function of β2-glycoprotein I in Angiogenesis and Its in Vivo Distribution in Tumor Xenografts.
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 β2GPI's 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.
authors.affiliation: Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Arum Tri
authors.initials: AT
authors.lastname: Wahyuningsih
authors.forename: Lianhua
authors.initials: L
authors.lastname: Shen
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Takanori
authors.initials: T
authors.lastname: Sasaki
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Takenaka
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hanada
authors.forename: Masaru
authors.initials: M
authors.lastname: Akehi
authors.forename: Akiya
authors.initials: A
authors.lastname: Akahoshi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ozeki
authors.forename: Eiji
authors.initials: E
authors.lastname: Ando
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
mesh_terms: D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism; D049268:Positron-Emission Tomography; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D053482:beta 2-Glycoprotein I / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D042442:Vascular Endothelial Growth Factors; D053482:beta 2-Glycoprotein I