TY - JOUR
T1 - Plasmin-cleaved β-2-glycoprotein 1 is an inhibitor of angiogenesis
AU - Sakai, Taro
AU - Balasubramanian, Krishnakumar
AU - Maiti, Sourindra
AU - Halder, Jyotsna B.
AU - Schroit, Alan J.
N1 - Funding Information:
Supported by the National Institutes of Health (grant CA-98527 ), the Department of Defense (grant PC030875 ), and the John Q. Gaines Foundation.
PY - 2007/11
Y1 - 2007/11
N2 - β-2-Glycoprotein 1, an abundant plasma glycoprotein, binds anionic cell surfaces and functions as a regulator of thrombosis. Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis. In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells. The protein was without effect on preformed endothelial cell tubes. In vivo, the cleaved protein inhibited neovascularization into subcutaneously implanted Matrigel and Gelfoam sponge implants and the growth of orthotopically injected tumors. Collectively, these data indicate that plasmin-cleaved β-glycoprotein 1 is a potent antiangiogenic and antitumor molecule of potential therapeutic significance.
AB - β-2-Glycoprotein 1, an abundant plasma glycoprotein, binds anionic cell surfaces and functions as a regulator of thrombosis. Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis. In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells. The protein was without effect on preformed endothelial cell tubes. In vivo, the cleaved protein inhibited neovascularization into subcutaneously implanted Matrigel and Gelfoam sponge implants and the growth of orthotopically injected tumors. Collectively, these data indicate that plasmin-cleaved β-glycoprotein 1 is a potent antiangiogenic and antitumor molecule of potential therapeutic significance.
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U2 - 10.2353/ajpath.2007.070146
DO - 10.2353/ajpath.2007.070146
M3 - Article
C2 - 17872974
AN - SCOPUS:36348947961
SN - 0002-9440
VL - 171
SP - 1659
EP - 1669
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -