Plasmin-cleaved beta-2-glycoprotein 1 is an inhibitor of angiogenesis.
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.
Sakai
Taro
T
The Department of Cancer Biology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA.
Balasubramanian
Krishnakumar
K
Maiti
Sourindra
S
Halder
Jyotsna B
JB
Schroit
Alan J
AJ
D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005341:Fibrinolysin / Q000502:physiology*; D005781:Gelatin Sponge, Absorbable; D018082:Kringles; D007797:Laminin; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology; D009389:Neovascularization, Pathologic; D011509:Proteoglycans; D053482:beta 2-Glycoprotein I / Q000494:pharmacology / Q000502:physiology*
D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D053482:beta 2-Glycoprotein I; C059485:matrigel; D003094:Collagen; D005341:Fibrinolysin