Suppression of urokinase-type plasminogen activator expression from human ovarian cancer cells by urinary trypsin inhibitor

Urinary trypsin inhibitor (UTI), a Kunitz-type protease inhibitor, efficien tly inhibits tumor cell invasion and metastasis. We examined the effect of UTI on urokinase-type plasminogen activator (uPA) expression in ovarian can cer cell lines, HOC-I and HRA. By Northern blot, Western blot, ELISA, and z ymographic analyses, we demonstrated that UTI inhibited the expression of u PA mRNA and protein in these cells in a time- and dose-dependent manner, in dependent of whether induction was triggered by phorbol ester. Monoclonal a ntibody 4G12, which inhibits Un binding to the cells, produced a dose-depen dent abrogation in UTI-mediated down-regulation of uPA expression. These da ta suggest that UTI significantly down-regulates tumor cell uPA mRNA expres sion and protein secretion, and that UTI binding to the cells is necessary to exert the UTI's action. (C) 2000 Elsevier Science B.V. All rights reserv ed.