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

CD95/APO-I ligand (Fast) is implicated in the maintenance of immune privile ged sites by inducing apoptosis of activated infiltrating T lymphocytes, Th erefore, progressive tumors might express high levels of Fast and develop a s immune privileged sites. In this study, we investigated the expression of Fast and CD95/APO-I (Fas, the Fast-receptor) in vitro in rat adenocarcinom a 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 i n vivo) expressed a higher level of Fast 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 apoptos is, In human tissue, both kidney and colon extracts expressed Fast by Weste rn blot, Further investigations, using immunohistochemical staining of para ffin sections, showed that normal colon mucosa expressed pas and Fast in cr ypt epithelial cells in the subnuclear compartment. Normal kidney showed Fa s and Fast labeling mostly restricted to epithelial cells of proximal tubul es 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 intensly but more uniformly labeled. In col oncancer cells, Fast expression remained strong, whereas Fas expression was significantly reduced. A similar reduction in Fas expression was noted in renal-cancer cells. Tumorinfiltrating immune cells of the macrophage lineag e do not express Fast. Our results show that smooth-muscle cells of muscula ris propria and blood vessels are able to express Fast and to a slight exte nt Fas. In normal epithelial cells of colon and kidney, Fas and Fast are of ten co-expressed. The reduced expression of Fas in corresponding cancer cel ls in combination with the ability to express Fast might facilitate immune escape, Int I. Cancer 81:772-778, 1999. (C) 1999 Wiley-Liss, Inc.