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, efficiently inhibits tumor cell invasion and metastasis. We examined the effect of UTI on urokinase-type plasminogen activator (uPA) expression in ovarian cancer cell lines, HOC-I and HRA. By Northern blot, Western blot, ELISA, and zymographic analyses, we demonstrated that UTI inhibited the expression of uPA mRNA and protein in these cells in a time- and dose-dependent manner, independent of whether induction was triggered by phorbol ester. Monoclonal antibody 4G12, which inhibits UTI binding to the cells, produced a dose-dependent abrogation in UTI-mediated down-regulation of uPA expression. These data suggest that UTI significantly down-regulates tumor cell uPA mRNA expression and protein secretion, and that UTI binding to the cells is necessary to exert the UTI's action.
Kobayashi
H
H
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Handacho 3600, Hamamatsu, 431-3192, Shizuoka, Japan.
Suzuki
M
M
Sun
G W
GW
Hirashima
Y
Y
Terao
T
T
D015536:Down-Regulation; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D006023:Glycoproteins; D012333:RNA, Messenger; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate; C028665:urinastatin