Inhibition of human tumor cell-associated fibrinolysis by vascular bovine smooth muscle cells.

Fibrinolysis induced by human tumor cells producing either urokinase (u-PA) or tissue-type plasminogen activators (t-PA) was inhibited by growth in vitro of the tumor cells together with aortic bovine smooth muscle cells (SMC). Both types of plasminogen activators secreted by the tumor cells were partially or completely neutralized in such cocultivation experiments. The fibrinolysis inhibitory activities were found in living SMC, homogenates of the cells, and medium conditioned by the SMC. Incubation of medium conditioned by the SMC with media conditioned by the tumor cells followed by polyacrylamide gel electrophoresis and regular fibrin zymography resulted in sodium dodecyl sulfate-resistant inhibition of fibrinolysis. Gel electrophoretic analysis of medium conditioned by SMC followed by reverse fibrin autography revealed the presence of a single zone of lysis inhibition that corresponded to a relative molecular weight of 51,500 +/- 1,700. These results demonstrate that SMC produce and secrete a powerful inhibitor of u-PA- and t-PA-induced fibrinolysis, which may alter the invasive and degradative potential of tumor cells.