Alterations in plasminogen activation correlate with epithelial cell dysplasia grading in colorectal adenomas

Autor: C. Trân-Thang, Gian Dorta, P. Chaubert, E. Saraga, P. Protiva, I. Sordat, A. L. Blum, Bernard Sordat
Rok vydání: 1998
Předmět:
Adenoma
Male
Cancer Research
Epithelial dysplasia
Pathology
medicine.medical_specialty
Tissue plasminogen activator
Adenoma/enzymology
Adenoma/pathology
Colorectal Neoplasms/enzymology
Colorectal Neoplasms/pathology
Enzyme Activation
Epithelial Cells/enzymology
Female
Fibrinolysin/metabolism
Humans
Middle Aged
Plasminogen/metabolism
Plasminogen Activator Inhibitor 1/metabolism
Plasminogen Activators/metabolism
Prospective Studies
Tissue Plasminogen Activator/metabolism
Urokinase-Type Plasminogen Activator/metabolism
chemistry.chemical_compound
Plasminogen Activators
Plasminogen Activator Inhibitor 1
medicine
Fibrinolysin
Urokinase
T-plasminogen activator
business.industry
Epithelial Cells
Plasminogen
medicine.disease
Urokinase-Type Plasminogen Activator
Oncology
chemistry
Dysplasia
Plasminogen activator inhibitor-1
Tissue Plasminogen Activator
business
Colorectal Neoplasms
Plasminogen activator
medicine.drug
Research Article
Zdroj: British Journal of Cancer
British journal of cancer, vol. 77, no. 2, pp. 297-304
ISSN: 0007-0920
Popis: Proteases are important for neoplastic invasion but a specific role for the plasminogen activator system in the progression of colorectal epithelial dysplasia to adenomatous lesions remains unclear. Consecutive tissue cryosections of 51 adenomas, 49 distant mucosa samples and five mucosa samples from control subjects were histopathologically analysed for dysplasia grade and tissue type, urokinase plasminogen activator levels and plasminogen activator inhibitor type 1 (PAI-1) using immunosorbent methods. Plasminogen activation and urokinase-mediated proteolytic activity levels were assessed using in situ zymography. Plasminogen activation and tissue-type activator levels were lower in adenomas than in mucosae (P < 0.001). PAI-1 concentration and urokinase levels were higher in adenomas than in mucosae (P < 0.001 and P < 0.001 respectively). In adenomas, urokinase concentration increased in parallel with PAI-1, but only the urokinase levels correlated with the dysplasia grade (P < 0.01). Thus, the alterations in plasminogen activation correlated with epithelial cell dysplasia grading. In the mucosa to adenoma transition, a marked decrease in tissue-type plasminogen activator occurred. In adenomas, this decrease was accompanied by a concomitant increase in urokinase and PAI-1. The urokinase level only continued to rise in parallel with the dysplasia grade. Resulting protease-antiprotease imbalance in high-grade dysplasia may represent the phenotypic change associated with malignant transformation and invasive behaviour. Images Figure 2
Databáze: OpenAIRE