Thrombin is a serine protease that is produced during the coagulation process and plays an essential role for hemostasis, thrombosis and wound healing. It is a potent activator of platelets, induces proliferation of a wide variety of normal and malignant human cells, and enhances their invasiveness and metastatic potential. We studied the effect of thrombin on the proliferation of a wide variety of human tumor cells and report here that, at low concentrations, thrombin induces proliferation of these cells. However, at higher concentrations, thrombin inhibited their proliferation. We show that this inhibition of cell proliferation was due to apoptosis of the tumor cells. The thrombin-mediated apoptosis was inhibited significantly by its specific inhibitor, hirudin. Furthermore, no consistent pattern of induction and/or modulation of p53, p21 and bcl-2 was observed in the thrombin-mediated apoptosis. To our knowledge, this is the first report to describe the pro-apoptotic effects of thrombin on human tumor cells and may have implications for chemotherapy in cancer patients and for the pathogenesis of AIDS as well.
Copyright 2000 Wiley-Liss, Inc.