Journal Article The Function of β2-glycoprotein I in Angiogenesis and Its in Vivo Distribution in Tumor Xenografts

Arum Tri Wahyuningsih,  ,  Shen, Lianhua  ,  Kobayashi, Kazuko  ,  Sasaki, Takanori  ,  Takenaka, Fumiaki  ,  Hanada, Takahisa  ,  Akehi, Masaru  ,  Akahoshi, Akiya  ,  Ozeki, Eiichi  ,  Ando, Eiji  ,  Matsuura, Eiji

70 ( 1 )  , pp.13 - 24 , 2016-02 , Okayama University Medical School
ISSN:0386-300X
NCID:AA00508441
Description
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.
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http://ousar.lib.okayama-u.ac.jp/files/public/5/53999/20160528120830913707/70_1_13.pdf

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