A novel immunocytolytic factor secreted by pancreatic adenocarcinoma

Background. me have observed a putative immunocytolytic factor secreted by several pancreatic adeno carcinoma cell lines that mediates a potent cytoly tic effect on lymphocytes. We sought to investigate its mechanism of action and determine if it is Fas ligand (FasL)-mediated. Materials and methods. Coincubation assays with murine splenocytes and supe rnatants from various species of pancreatic adenocarcinoma cell lines were performed. The mechanism of lymphocytic cell death was evaluated by the TUN EL assay. Pancreatic adenocarcinoma supernatant was coincubated with Fas-se nsitive Jurkat cells and Western blotting for Fast was performed. Results. A marked reduction in the viability (%/control) of target splenocy tes was observed after incubation with the conditioned media from hamster P AN-1 (14.7%), PC 1.0 (21.7%), Taka-1 p70 (12.4%), Taka-1 p79 (7.6%), murine PANCO2 (16.1%), and human Capan-1 (14.0%) pancreatic adenocarcinoma cell l ines. FACS analysis demonstrated significant lymphoid apoptosis at 16 h. Th e cytolytic effect appeared to be specific for lymphocytes and was not obse rved with the conditioned media of other tumor cells or normal pancreatic d uctal cells. Pancreatic adenocarcinoma supernatant had no killing effect on Jurkat cells compared with control supernatant of TC-248 cells (87% vs 15% ) and immunoblotting did not demonstrate soluble FasL. Conclusions. These findings demonstrate that pancreatic adenocarcinoma cell s secrete a potent cytolytic factor that induces apoptosis of lymphocytes a nd is not FasL-mediated. (C) 2000 Academic Press.