BINDING AND BIOLOGICAL EFFECTS OF TUMOR-NECROSIS-FACTOR AND GAMMA-INTERFERON IN HUMAN PANCREATIC-CARCINOMA CELLS

The cytotoxic/cytostatic effects of recombinant human tumor necrosis factor alpha (rhTNF) and gamma interferon (rhlFN-γ) were studied in five human pancreatic tumor cell lines. During a 48-h incubation, MIA PaCa-2 cells were most sensitive to rhTNF (56% cytotoxicity, 500 U/ml), T3M4cells were most sensitive to rhIFN-γ (54% cytostasis, 250 U/ml), and ASPC-1 and COLO 357 cells were most sensitive to the combination of rhTNF and rhIFN-γ (56 and 55% cytotoxicity, respectively, 250 U/ml of each cytokine). The PANC-1 cells were relatively insensitive to either the individual or the combined effects of these cytokines. All five cell lines exhibited specific, high-affinity receptors for125I-labeled rhTNF (480-8,610 sites/cell) and rhIFN-γ (2,050-6,280 sites/cell). The MIA PaCa-2 cells, which were the most sensitive to the inhibitory effects of rhTNF, also possessed the largest number of 12SI rhTNF receptors; all other cell lines had a relatively low number of binding sites and low sensitivity. In contrast, no direct correlation could be made between the number of IFN-7 binding sites and inhibitory sensitivity in any of the cell lines. Incubation of COLO 357 cells at 37°C with either125I rhTNF or 125I rhINF-7 led to internalization of the respective125I-labeled ligand. Our findings document the presence of cytokine receptors in human pancreatic carcinoma cells and suggest that postreceptor events rather than differences in receptor number or affinity more likely govern the responsiveness of pancreatic cancer cells to TNF and IFN-7. © 1990 Raven Press, New York.