Thrombin induces apoptosis in human tumor cells

Thrombin is a serine protease that is produced during the coagulation proce ss and plays an essential role for hemostasis, thrombosis and wound healing . It is a potent activator of platelets, induces proliferation of a wide va riety of normal and malignant human cells, and enhances their invasiveness and metastatic potential. We studied the effect of thrombin on the prolifer ation of a wide variety of human tumor cells and report here that, at low c oncentrations, thrombin induces proliferation of these cells. However, at h igher concentrations, thrombin inhibited their proliferation. We show that this inhibition of cell proliferation was due to apoptosis of the tumor cel ls. The thrombin-mediated apoptosis was inhibited significantly by its spec ific inhibitor, hirudin. Furthermore, no consistent pattern of induction an d/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 implication s for chemotherapy in cancer patients and for the pathogenesis of AIDS as w ell. (C) 2000 Wiley-Liss, Inc.