Novel Function of Beta 2 Glycoprotein I in Angiogenesis

Author(s): Hisako Nakagawa, Shinsuke Yasuda, Tadaaki Miyazaki.

Journal Name: Current Angiogenesis (Discontinued)

Volume 3 , Issue 3 , 2014

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Abstract:

β2-glycoprotein I (β2GPI) is an important autoantigen in patients with antiphospholipid syndrome (APS), an autoimmune disorder characterized by thrombosis and pregnancy morbidity. β2GPI is able to bind to anionic phospholipid via the lysine cluster and hydrophobic loop in the domain V Cys281-Cys288 region. It also binds annexin II, oxLDL, and apoptotic cells. As a result β2GPI plays a role in a broad range of pleiotropic functions affecting coagulation/fibrinolysis, angiogenesis, lipid metabolism, and apoptosis. β2GPI is cleaved by plasmin and activated factor XI. This cleaved form of β2GPI is designated as nicked β2GPI and is unable to bind phospholipids. β2GPI and nicked β2GPI play essential roles to inhibit VEGF/FGF-induced angiogenesis via its domain I. We have reported that nicked β2GPI binds to the angiostatin kringle 4.5 via its domain V and exerts a pro-angiogenic effect in vitro and in vivo. Several studies have demonstrated that the antiangiogenic effects of β2GPI mainly depend on the inhibition of the VEGF-VEGFR2 pathway signaling. Since angiogenesis is an essential component in tumor growth and metastasis, controlling tumor-angiogenesis is an effective strategy to inhibit tumor development. Thus far, VEGF/VEGFR targeted agents such as bevacizumab, sorafenib, and sunitinib have been shown effectively in prolong survival for some cancer patients. Briefly, β2GPI offers the potential to become a suppressor of tumor angiogenesis and an inhibitor of cancer progression. In this review, we focus on the antiangiogenic effect of intact/nicked β2GPI, and discuss how it may be related to tumor angiogenesis and/or tumor metastasis inhibition.

Keywords: Angiogenesis, blood vessel, beta-2 Glycoprotein I, coagulation/fibrinolysis, HUVECs and tumorigenesis.

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Article Details

VOLUME: 3
ISSUE: 3
Year: 2014
Page: [132 - 138]
Pages: 7
DOI: 10.2174/2211552803666141125214938
Price: $58

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