Abstract
beta-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 beta-2-glycoprotein 1 is a potent antiangiogenic and antitumor molecule of potential therapeutic significance.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Cell Movement / drug effects
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Cells, Cultured
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Collagen
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Drug Combinations
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Endothelial Cells / drug effects
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Endothelial Cells / physiology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / physiology
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Fibrinolysin / physiology*
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Gelatin Sponge, Absorbable
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Kringles
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Laminin
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Molecular Sequence Data
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Neoplasm Transplantation
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Neoplasms, Experimental / blood supply
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Neoplasms, Experimental / pathology
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Neovascularization, Pathologic*
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Proteoglycans
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beta 2-Glycoprotein I / pharmacology
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beta 2-Glycoprotein I / physiology*
Substances
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Angiogenesis Inhibitors
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Drug Combinations
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Laminin
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Proteoglycans
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beta 2-Glycoprotein I
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matrigel
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Collagen
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Fibrinolysin