Cited 47 times since 1991 (1.4 per year) source: EuropePMC Gastroenterology, Volume 101, Issue 6, 1 1 1991, Pages 1522-1528 Imbalance of plasminogen activators and their inhibitors in human colorectal neoplasia. Implications of urokinase in colorectal carcinogenesis. Sier CF, Verspaget HW, Griffioen G, Verheijen JH, Quax PH, Dooijewaard G, De Bruin PA, Lamers CB
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.
