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A novel immunocytolytic factor secreted by pancreatic adenocarcinoma
L P Angel1, C M Divino, S T Brower
1Division of Surgical Oncology, Institute for Gene Therapy and Molecular Medicine, New York, New York 10029-6574, USA.
Background:
We have observed a putative immunocytolytic factor secreted by several pancreatic adenocarcinoma cell lines that mediates a potent cytolytic 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 supernatants from various species of pancreatic adenocarcinoma cell lines were performed. The mechanism of lymphocytic cell death was evaluated by the TUNEL assay. Pancreatic adenocarcinoma supernatant was coincubated with Fas-sensitive Jurkat cells and Western blotting for FasL was performed.
Results:
A marked reduction in the viability (%/control) of target splenocytes was observed after incubation with the conditioned media from hamster PAN-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 lines. FACS analysis demonstrated significant lymphoid apoptosis at 16 h. The cytolytic effect appeared to be specific for lymphocytes and was not observed with the conditioned media of other tumor cells or normal pancreatic ductal 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 cells secrete a potent cytolytic factor that induces apoptosis of lymphocytes and is not FasL-mediated.