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Binding of the urokinase-type plasminogen activator to its cell surface receptor is inhibited by low doses of suramin

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The multipotent drug suramin, which is currently being studied as an anticancer agent, was found to inhibit the interaction between the urokinase-type plasminogen activator (u-PA) and its cellular receptor. 50% inhibition of binding was obtained with a suramin concentration between 30 and 60 micrograms/ml when using U937 cells and a ligand concentration of 0.3 nM. This concentration of the drug is well below the serum levels found in suramin-treated patients. Inhibition of binding was also demonstrated at the molecular level, using chemical cross-linking or an enzyme-linked immunosorbent assay-type technique based on the ligand interaction. The inhibition was not caused by a mere polyanion effect since polysulfates such as heparin, heparan sulfate, and pentosan polysulfate were non-inhibitory or showed only a very weak inhibition. However, polysulfonated compounds with structures resembling suramin (i.e. trypan blue and Evans blue) did prove inhibitory. The inhibition found with suramin showed a concentration dependence consistent with a mixed competitive and noncompetitive mechanism. The off-rate of prebound ligand was accelerated by the drug. It is speculated that the present effect may contribute to the anti-invasive properties of suramin by destroying the cellular potential for localized plasminogen activation and proteolytic matrix degradation.

Original languageEnglish
JournalThe journal of biological chemistry
Volume268
Issue number8
Pages (from-to)5985-9
Number of pages5
ISSN0021-9258
Publication statusPublished - 15 Mar 1993

    Research areas

  • Binding, Competitive, Cell Membrane, Cells, Cultured, Cross-Linking Reagents, Enzyme-Linked Immunosorbent Assay, Humans, Receptors, Cell Surface, Receptors, Urokinase Plasminogen Activator, Suramin, Urokinase-Type Plasminogen Activator

ID: 46434812