Production and pro-apoptotic activity of soluble CD95 ligand in pancreaticcarcinoma

We report here that the progression of pancreatic carcinomas In tumor patie nts is associated with increased serum levels of both the soluble forms of CD95 ligand (CD95L/FasL) and its receptor, CD95 (Fas), Shedding of proteoly tically processed soluble CD95L was also observed in pancreatic carcinoma c ells in vitro, thus identifying one possible source of CD95L in patients' s era. Because the secreted forms of both CD95 and CD95L have been implicated previously in protection of cells from CD95-mediated cell death, we assess ed the effect of soluble CD95L in supernatants of pancreatic carcinoma cell s on viability of Jurkat T lymphocytes, We describe that (a) supernatants d erived from cultured pancreatic carcinoma cells caused apoptosis of Jurkat cells; (b) soluble tumor-derived CD95L contributed significantly to this ef fect; and (c) in comparison to Jurkat cells, pancreatic carcinoma cells the mselves revealed increased resistance to apoptosis induction by autocrine s oluble CD95L, These results are consistent,vith the notion that in the micr oenvironment of pancreatic tumors, tumor-derived shed CD95L exerts pancreat ic pro-apoptotic effects, In addition, because it is released at high level s into the bloodstream, soluble CD95L may have systemic effects in tumor pa tients that reach beyond the microenvironment of the tumor site.