SURAMIN, AN ANTICANCER AND ANGIOSUPPRESSIVE AGENT, INHIBITS ENDOTHELIAL-CELL BINDING OF BASIC FIBROBLAST GROWTH-FACTOR, MIGRATION, PROLIFERATION, AND INDUCTION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR

Suramin, an anticancer agent in current clinical trials, is a prototyp e of a pharmacological antagonist of growth factors, including basic f ibroblast growth factor (bFGF). Suramin inhibited angiogenesis in the chick chorioallantoic membrane assay in a dose-dependent fashion. Sura min, 200 mg/kg i.v., inhibited rat corneal angiogenesis induced by bFG F-impregnated polymers; addition of heparin stimulated angiogenesis an d counteracted the inhibition of suramin. The half-maximal inhibitory concentration (IC50) of suramin was determined for key cellular mechan isms that regulate angiogenesis: (a) low and high af- finity cellular binding of bFGF to bovine capillary endothelial (BCE) cells with IC(50 )s, respectively, of 24.3 and 71.5 mu g/ml; (b) spontaneous migration of bovine pulmonary artery endothelial and normal AG 7680 fetal bovine aortic endothelial cells; bFGF-stimulated migration of BCE and transf ormed GM 7373 fetal bovine aortic endothelial cells with IC(50)s of 20 0-320 mu g/ml; (c) proliferation of bovine pulmonary artery endothelia l cells at >100 mu g/ml and of BCE cells at >250 mu g/ml; and (d) urok inase-type plasminogen activator activity of GM 7373 endothelial cells stimulated by bFGF with an IC50 of 211 mu g/ml and of BCE cells stimu lated by bFGF at >100 mu g/ml, but not plasminogen activator activity induced by phorbol 12-myristate 13-acetate. Suramin inhibited multiple control points of angiogenesis, including those stimulated by bFGF. B ecause tumor growth is angiogenesis dependent, the clinical efficacy o f suramin may relate, in part, to angiosuppression.