Modulation of human colon tumor-stromal interactions by the endothelin system

Details

Serval ID
serval:BIB_5366065C3612
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Modulation of human colon tumor-stromal interactions by the endothelin system
Journal
American Journal of Pathology
Author(s)
Egidy  G., Juillerat-Jeanneret  L., Jeannin  J. F., Korth  P., Bosman  F. T., Pinet  F.
ISSN
0002-9440 (Print)
Publication state
Published
Issued date
2000
Volume
157
Number
6
Pages
1863-1874
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Abstract
Tumor neovascularization is considered to be a critical step in the development of a malignant tumor. Endothelin (ET)-1 is a powerful vasoconstrictor and mitogenic peptide that is produced by many cancer cell lines. The cellular distribution of the ET components was evaluated in human colon tumors and compared to normal colon. There was more of the ET components (preproET-1, endothelin-converting enzyme-1, and ETA and ETB receptors) in adenomas and adenocarcinomas than in the normal colon. There was overproduction of preproET-1 and endothelin-converting enzyme-1 in carcinoma cells and stromal vessels, suggesting that they are a local source of ET-1. ETA receptors were present in stromal myofibroblasts of neoplastic tissue, and there were large amounts of ETB receptors in the endothelium and myofibroblasts. There was also a redistribution of alpha-smooth muscle actin-positive cells in the vascular structures of tumors. An experimental rat model of induced colon cancer treated for 30 days with bosentan, a mixed antagonist of both ET receptors, confirmed the morphological changes observed during the tumor vascularization. Our data suggest that ET-1 and its receptor play a role in colon cancer progression, with ET-1 functioning as a negative modulator of the stromal response
Keywords
Adenocarcinoma/metabolism/Pathology/Adult/Aged/Aged,80 and over/Animals/Aspartic Endopeptidases/genetics/Colon/Colonic Neoplasms/Endothelin-1/Endothelins/Female/Humans/Male/Metalloendopeptidases/Middle Aged/Protein Precursors/RNA,Messenger/Rats/Rats,Inbred Strains/Receptor,Endothelin A/Receptor,Endothelin B/Receptors,Endothelin/antagonists & inhibitors/Reference Values/Sulfonamides/pharmacology/Tissue Distribution
Pubmed
Web of science
Create date
29/01/2008 18:33
Last modification date
20/08/2019 14:08
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