title: Imbalance of plasminogen activators and their inhibitors in human colorectal neoplasia. Implications of urokinase in colorectal carcinogenesis.
abstract: Neoplastic growth and metastatic spread of adenocarcinomas is characterized by a marked increase of urokinase-type plasminogen activator (u-PA) and a decrease of tissue-type plasminogen activator (t-PA). In this study, the authors determined the activity and antigen levels of u-PA and t-PA, and their inhibitors, plasminogen-activator inhibitors types 1 and 2 (PAI-1 and PAI-2), in normal mucosa, adenomatous polyps, and adenocarcinomas of the human colon. The decrease in t-PA activity in the neoplastic tissues, determined enzymatically and zymographically, was significantly correlated with an increase in PAI-1 and PAI-2, in particular in carcinomas. In spite of significantly higher inhibitor levels in the neoplastic tissues, u-PA was found to be increased as well, both in antigen level and in activity. The authors conclude that PAI-1 and PAI-2 are significantly increased in neoplastic tissue of the human colon and contribute considerably to the decrease of t-PA activity in carcinomas. However, the malignancy-associated increase in u-PA seems not to be affected by the plasminogen activator inhibitors. Thus, it appears that there is an imbalance between plasminogen activators and their inhibitors in colonic neoplasia in favor of u-PA, which may contribute to plasmin-mediated growth, invasiveness, and metastasis. This feature was also noticed in adenomatous polyps, supporting the malignant potency of adenomas.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital, Leiden, The Netherlands.
authors.forename: C F
authors.initials: CF
authors.lastname: Sier
authors.forename: H W
authors.initials: HW
authors.lastname: Verspaget
authors.forename: G
authors.initials: G
authors.lastname: Griffioen
authors.forename: J H
authors.initials: JH
authors.lastname: Verheijen
authors.forename: P H
authors.initials: PH
authors.lastname: Quax
authors.forename: G
authors.initials: G
authors.lastname: Dooijewaard
authors.forename: P A
authors.initials: PA
authors.lastname: De Bruin
authors.forename: C B
authors.initials: CB
authors.lastname: Lamers
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000941:Antigens / Q000032:analysis; D003106:Colon / Q000737:chemistry*; D003111:Colonic Polyps / Q000737:chemistry*; D015179:Colorectal Neoplasms / Q000737:chemistry*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D015849:Plasminogen Inactivators / Q000032:analysis* / Q000276:immunology; D010959:Tissue Plasminogen Activator / Q000032:analysis*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
chemical_list: D000941:Antigens; D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator