Journal Article

Increased levels of cathepsin B and L, urokinase-type plasminogen activator and its inhibitor type-1 as an early event in gastric carcinogenesis

F. Farinati, L. Herszènyi, M. PIebani, P. Carraro, M. De Paoli, R. Cardin, G. Roveroni, M. Rugge, D. Nitti, W.F. Grigioni, A. D'Errico and R. Naccarato

in Carcinogenesis

Volume 17, issue 12, pages 2581-2587
Published in print December 1996 | ISSN: 0143-3334
Published online December 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.12.2581
Increased levels of cathepsin B and L, urokinase-type plasminogen
                    activator and its inhibitor type-1 as an early event in gastric
                    carcinogenesis

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Background

Cysteine proteases [cathepsin B (CATB), cathepsin L (CATL)], the serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type-1 (PAI-1) play an important part in cancer invasion. No data are available on the relationship between these proteases and gastric precancerous changes. Aims: To determine CATB, CATL, UPA, PAI-1 in chronic atrophic gastritis, intestinal metaplasia and gastric epithelial dysplasia, as precancerous changes, and to compare these data with those obtained hi gastric cancer. Patients: Endoscopic biopsies were obtained from 12 patients with gastric cancer (cancerous tissue), 33 patients with chronic atrophic gastritis (all with intestinal metaplasia and 12 with dysplasia) and from 47 control subjects, for a total of 92 patients. Methods: Antigen concentrations were measured using ELISA methods. Immunohistochemistry was performed using monoclonal anti-CATB and anti-PAI-1 antibodies. Results: CATB, CATL, UPA and PAI-1 were significantly higher in chronic atrophic gastritis than in controls (CATB: P < 0.001; CATL: P < 0.005; UPA: P < 0.000001; PAI-1: P < 0.005). The same was observed for cancer. CATB and UPA were significantly higher in chronic atrophic gastritis, with versus without dysplasia (P < 0.05). Dysplastic epithelia showed strong immunoreactivity to PAI-1 and CATB. Conclusions: Our study demonstrates that cathepsins, UPA and PAI-1 may have a role not only in the process of cancer invasion, but also in the progression of precancerous changes into cancer.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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