A novel disintegrin salmosin inhibits tumor angiogenesis.
Salmosin is a snake venom-derived novel disintegrin that antagonizes platelet aggregation. In this study, we investigated its functional specificity in tumor angiogenesis. Salmosin significantly inhibited bovine capillary endothelial cell proliferation induced by basic fibroblast growth factor but had no effect on normal growth of the cell. The basic fibroblast growth factor-induced in vivo angiogenesis in the chorioallantoic membrane was disrupted by salmosin treatment without affecting normal embryonic angiogenesis. Adhesion of the bovine capillary endothelial cells to vitronectin was also inhibited by the binding of salmosin to the alpha(v)beta3 integrin. Both the metastatic-tumor growth and the solid-tumor growth that developed in mice were effectively suppressed by salmosin treatment. Several lines of experimental evidence strongly suggest that the tumor-specific antiangiogenic activity of salmosin disrupts tumor growth by blocking the alpha(v)beta3 integrin that is expressed on the vascular endothelial cell surface.
Kang
I C
IC
Department of Biochemistry, College of Science, and Bioproducts Research Center, Yonsei University, Seoul, Korea.
Lee
Y D
YD
Kim
D S
DS
D000482:Allantois / Q000098:blood supply / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002277:Carcinoma / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects; D003435:Crotalid Venoms / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009842:Oligopeptides; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000637:transplantation; D019096:Vitronectin / Q000378:metabolism
D000970:Antineoplastic Agents; D003435:Crotalid Venoms; D009363:Neoplasm Proteins; D009842:Oligopeptides; D019030:Receptors, Vitronectin; D019096:Vitronectin; C115393:salmosin; D016222:Fibroblast Growth Factor 2; C047981:arginyl-glycyl-aspartic acid