The function of β2-glycoprotein I in angiogenesis and its in vivo distribution in tumor xenografts

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)13-24
Number of pages12
JournalActa Medica Okayama
Volume70
Issue number1
Publication statusPublished - 2016

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Keywords

  • Angiogenesis
  • Positron emission tomography (PET) imaging
  • Vascular endothelial growth factor-A (VEGF-A)
  • β2-glycoprotein I (β2GPI)

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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