Published online before print September 14, 2007

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(American Journal of Pathology. 2007;171:1659-1669.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.070146

Plasmin-Cleaved ß-2-Glycoprotein 1 Is an Inhibitor of Angiogenesis

From the Department of Cancer Biology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas

ß-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 ß-2-glycoprotein 1 is a potent antiangiogenic and antitumor molecule of potential therapeutic significance.