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

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_BCFB0C162F82
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Alterations in plasminogen activation correlate with epithelial cell dysplasia grading in colorectal adenomas.
Journal
British journal of cancer
Author(s)
Protiva P., Sordat I., Chaubert P., Saraga E., Trân-Thang C., Sordat B., Blum A.L., Dorta G.
ISSN
0007-0920 (Print)
ISSN-L
0007-0920
Publication state
Published
Issued date
1998
Peer-reviewed
Oui
Volume
77
Number
2
Pages
297-304
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.

Keywords
Adenoma/enzymology, Adenoma/pathology, Colorectal Neoplasms/enzymology, Colorectal Neoplasms/pathology, Enzyme Activation, Epithelial Cells/enzymology, Female, Fibrinolysin/metabolism, Humans, Male, Middle Aged, Plasminogen/metabolism, Plasminogen Activator Inhibitor 1/metabolism, Plasminogen Activators/metabolism, Prospective Studies, Tissue Plasminogen Activator/metabolism, Urokinase-Type Plasminogen Activator/metabolism
Pubmed
Web of science
Create date
25/01/2008 16:48
Last modification date
20/08/2019 16:31
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