Fas and Fas ligand expression in tumor cells and in vascular smooth-muscle cells of colonic and renal carcinomas


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Fas and Fas ligand expression in tumor cells and in vascular smooth-muscle cells of colonic and renal carcinomas
International Journal of Cancer
Peduto Eberl  L., Guillou  L., Saraga  E., Schroter  M., French  L. E., Tschopp  J., Juillerat-Jeanneret  L.
0020-7136 (Print)
Statut éditorial
Date de publication
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May 31
CD95/APO-1 ligand (FasL) is implicated in the maintenance of immune privileged sites by inducing apoptosis of activated infiltrating T lymphocytes. Therefore, progressive tumors might express high levels of FasL and develop as immune privileged sites. In this study, we investigated the expression of FasL and CD95/APO-1 (Fas, the FasL-receptor) in vitro in rat adenocarcinoma cell lines and the localization in situ in normal human kidney and colon and in their adenocarcinomas. The rat cell line PROb (a progressive tumor in vivo) expressed a higher level of FasL than the sister cell line REGb (a regressive tumor in vivo), as detected by flow cytometry. The 2 cell lines expressed the same level of Fas, but were resistant to FasL-induced apoptosis. In human tissue, both kidney and colon extracts expressed FasL by Western blot. Further investigations, using immunohistochemical staining of paraffin sections, showed that normal colon mucosa expressed Fas and FasL in crypt epithelial cells in the subnuclear compartment. Normal kidney showed Fas and FasL labeling mostly restricted to epithelial cells of proximal tubules and Henle's loop, showing that this expression is not uniform throughout the organ. Smooth-muscle cells of muscularis propria and blood vessels in and around the tumors were also intensely but more uniformly labeled. In colon-cancer cells, FasL expression remained strong, whereas Fas expression was significantly reduced. A similar reduction in Fas expression was noted in renal-cancer cells. Tumor-infiltrating immune cells of the macrophage lineage do not express FasL. Our results show that smooth-muscle cells of muscularis propria and blood vessels are able to express FasL and to a slight extent Fas. In normal epithelial cells of colon and kidney, Fas and FasL are often co-expressed. The reduced expression of Fas in corresponding cancer cells in combination with the ability to express FasL might facilitate immune escape.
Adenocarcinoma/blood supply/*metabolism Animals Antigens, CD95/*biosynthesis Blotting, Western Carcinoma, Renal Cell/blood supply/*metabolism Colon/blood supply/metabolism Colonic Neoplasms/blood supply/*metabolism Fas Ligand Protein Flow Cytometry Humans Immunohistochemistry Intestinal Mucosa/blood supply/metabolism Kidney/blood supply/metabolism Kidney Neoplasms/blood supply/*metabolism Membrane Glycoproteins/*biosynthesis Muscle, Smooth, Vascular/blood supply/*metabolism Rats Tumor Cells, Cultured
Création de la notice
24/01/2008 16:18
Dernière modification de la notice
20/08/2019 16:46
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