Imbalance of plasminogen activators and their inhibitors in human colorectal neoplasia. Implications of urokinase in colorectal carcinogenesis.
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.
Sier
C F
CF
Department of Gastroenterology and Hepatology, University Hospital, Leiden, The Netherlands.
Verspaget
H W
HW
Griffioen
G
G
Verheijen
J H
JH
Quax
P H
PH
Dooijewaard
G
G
De Bruin
P A
PA
Lamers
C B
CB
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*
D000941:Antigens; D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator