Mitogenic effect of urokinase on malignant and unaffected adjacent human renal cells

Primary cultures of renal cell carcinomas and of the corresponding normal adjacent kidney tissue from 6 patients were analyzed for the effects of exogenously added urokinase-type plasminogen activator on cell proliferation as compared to the effects of tissue type plasminogen activator, plasmin and dihydrocortisone. Cell proliferation was studied over a period of up to 5 days by measuring 3H-thymidine incorporation as well as cell viability and cell count; conditioned media of the cultures were also analyzed for their plasminogen activator and plasminogen activator inhibitor content. Addition of urokinase stimulated cell proliferation in a time and dose dependent fashion; after 3 days 3H-thymidine incorporation was significantly increased in malignant renal cells (188.3 +/- 28.7%), while it reached in normal renal cells approximately 130% of the 3H-thymidine incorporation of untreated cultures. Tissue-type plasminogen activator had no effect and plasmin decreased cell proliferation slightly while dihydrocortisone inhibited cell proliferation significantly (34.1 +/- 4.9%) in malignant cells. It is concluded that urokinase-type plasminogen activator itself exhibits a mitogenic effect also on primary cultures of renal cell carcinomas.