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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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| Author(s): BEHRENDT N, RONNE E, DANO K |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 268 Issue: 8 Pages: 5985-5989 Published: MAR 15 1993 |
| Times Cited: 34 References: 42 |
| Abstract: 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 mug/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. |
| Document Type: Article |
| Language: English |
| Reprint Address: BEHRENDT, N (reprint author), RIGSHOSP, FINSEN LAB, STRANDBLVD 49 862, DK-2100 COPENHAGEN, DENMARK |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: KR822 |
| ISSN: 0021-9258 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |