Imbalance of plasminogen activators and their inhibitors in human colorectal neoplasia. Implications of urokinase in colorectal carcinogenesis
- C F Sier 1, H W Verspaget , G Griffioen , J H Verheijen , P H Quax , G Dooijewaard , P A De Bruin , C B Lamers
- 1Department of Gastroenterology and Hepatology, University Hospital, Leiden, The Netherlands.
- 0Department of Gastroenterology and Hepatology, University Hospital, Leiden, The Netherlands.
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View abstract on PubMed
Summary
This summary is machine-generated.Colorectal cancer growth involves increased urokinase-type plasminogen activator (u-PA) and decreased tissue-type plasminogen activator (t-PA). Inhibitors PAI-1 and PAI-2 rise, but u-PA remains elevated, favoring tumor spread.
Area Of Science
- Biochemistry
- Oncology
- Molecular Biology
Background
- Adenocarcinomas exhibit altered plasminogen activator (PA) activity, with increased urokinase-type (u-PA) and decreased tissue-type (t-PA).
- Plasminogen activator inhibitors (PAIs) like PAI-1 and PAI-2 play regulatory roles in PA activity.
Purpose Of The Study
- To investigate the levels and activity of u-PA, t-PA, PAI-1, and PAI-2 in normal colon mucosa, adenomatous polyps, and adenocarcinomas.
- To elucidate the role of these components in the progression of colonic neoplasia.
Main Methods
- Enzymatic assays and zymography were used to determine PA activity.
- Antigen levels of u-PA, t-PA, PAI-1, and PAI-2 were quantified.
- Comparisons were made between normal mucosa, adenomas, and carcinomas.
Main Results
- t-PA activity significantly decreased in neoplastic tissues, correlating with increased PAI-1 and PAI-2, especially in carcinomas.
- u-PA antigen levels and activity were significantly elevated in neoplastic tissues, despite higher inhibitor concentrations.
- Adenomatous polyps showed similar trends, suggesting early malignant potential.
Conclusions
- PAI-1 and PAI-2 significantly contribute to the reduction of t-PA activity in colonic carcinomas.
- Elevated u-PA in colonic neoplasia appears independent of PA inhibitor levels.
- An imbalance favoring u-PA in colonic neoplasia may promote tumor growth, invasion, and metastasis.
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