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A Novel Disintegrin Salmosin Inhibits Tumor Angiogenesis¹

Department of Biochemistry, College of Science, and Bioproducts Research Center, Yonsei University, Seoul 120-749 [I-C. K., D-S. K.], and Department of Anatomy, Ajou University, School of Medicine, Suwon 442-749 [Y-D. L.], Korea

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 _vß₃ 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 _vß₃ integrin that is expressed on the vascular endothelial cell surface.

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