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Suramin, an Anticancer and Angiosuppressive Agent, Inhibits Endothelial Cell Binding of Basic Fibroblast Growth Factor, Migration, Proliferation, and Induction of Urokinase-Type Plasminogen Activator¹

Division of Neurological Surgery, Northwestern Memorial Hospital and School of Medicine, Chicago, Illinois, 60611-2906 [S. T., S. G., H. E., S. B.], and the Du Pont Merck Pharmaceutical Company, Wilmington, Delaware, 19880-0400 [M. E. N., W. F. H., J. L. G., M. P., K. E.]

Suramin, an anticancer agent in current clinical trials, is a prototype of a pharmacological antagonist of growth factors, including basic fibroblast growth factor (bFGF). Suramin inhibited angiogenesis in the chick chorioallantoic membrane assay in a dose-dependent fashion. Suramin, 200 mg/kg i.v., inhibited rat corneal angiogenesis induced by bFGF-impregnated polymers; addition of heparin stimulated angiogenesis and counteracted the inhibition of suramin. The half-maximal inhibitory concentration (IC₅₀) of suramin was determined for key cellular mechanisms that regulate angiogenesis: (a) low and high affinity cellular binding of bFGF to bovine capillary endothelial (BCE) cells with IC₅₀s, respectively, of 24.3 and 71.5 µg/ml; (b) spontaneous migration of bovine pulmonary artery endothelial and normal AG 7680 fetal bovine aortic endothelial cells; bFGF-stimulated migration of BCE and transformed GM 7373 fetal bovine aortic endothelial cells with IC₅₀s of 200–320 µg/ml; (c) proliferation of bovine pulmonary artery endothelial cells at >100 µg/ml and of BCE cells at >250 µg/ml; and (d) urokinase-type plasminogen activator activity of GM 7373 endothelial cells stimulated by bFGF with an IC₅₀ of 211 µg/ml and of BCE cells stimulated by bFGF at >100 µg/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. Because tumor growth is angiogenesis dependent, the clinical efficacy of suramin may relate, in part, to angiosuppression.

¹ This work was supported, in part, by grants from the Illinois Neurofibromatosis, Inc. (to S. T. and S. G.), Northwestern Memorial Foundation, NIH (CA57781, CA60177), and the Du Pont Merck Pharmaceutical Co. (to S. B.).

² To whom requests for reprints should be addressed, at Division of Neurological Surgery, Northwestern Memorial Hospital, 233 East Erie Street, Suite 500, Chicago, IL 60611-2906.

Received 6/ 1/93. Accepted 3/16/94.

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