Cell Culture. The PC-3cell line is a prostatecancercell line derivedfrom a lumbar vertebral metastasis of a poorly differentiated human prostatic ade

The presence of procoagulants and fibrin deposition have been dem onstrated in malignant tumors. Although thrombin, a key enzyme in coagulation, has other various biological functions, the significance of its presence in tumors is not known. We studied the effects of thrombin on the expression of urokinase-type plasminogen activator (uPA) which is known to play a role in tumor invasion, using a human prostate cancer cell line PC-3. Human a-thrombin added to cultures of PC-3 produced a dose-dependent and time-dependent increased secretion of uPA that was greatest at 3—6h after exposure to thrombin. Increase in uPA antigen paralleled the Increase in mRNA level, which reached a maximum at 4 h. Thrombin showed the maximum effect on uPA expression at a concen tratlon 1—2units/mL Zymography showed that transient exposure to thrombin induced an increase in fibrinolytic activity which could be quenched by anti-uPA antibody. The thrombin receptor-activating pep tide also caused an increase in uPA protein and mRNA level, indicating the presence of the same thrombin specific receptor on PC-3 cells as on platelets and endothelial cells. Thrombin did not affect the expression of other components of the plasminogen activation system, tissue-type plas minogen activator and type-i plasminogen activator inhibitor, and uPA receptor. These results Indicate that thrombin increases uPA expression selectively by the stimulation of a functional thrombin receptor on PC-3 cells. Since uPA is known to play a role in periceflular proteolysis of extracellular matrix, thrombin may be involved In the regulation of tumor invasion and metastasis.