Production of Prostaglandin E₂ by Tumor Cells in Vitro

Our previous observations on the production of prostaglandin E₂ (PGE₂) by bladder tumor cell lines in vitro and the enhancement of tumor cell PGE₂ production upon exposure to purified peripheral blood lymphocytes from normal human donors prompted us to examine this interaction in an animal model in order to further define conditions that determine the occurrence of this phenomenon. Cell lines derived from carcinogen-induced bladder and mammary tumors and from embryo fibroblasts in Fischer rats were exposed to purified peripheral blood or splenic lymphocytes in the presence or absence of indomethacin (10^-7 M). After varying times at 37°, supernatants were harvested for determination of PGE₂ by radioimmunoassay. Time course studies demonstrated rapid PGE₂ production with plateau levels appearing at 8 hr. Increased tumor cell PGE₂ production occurred in the presence of increased numbers of lymphocytes. Indomethacin partially inhibited PGE₂ production. Preincubation studies suggested that the contribution of lymphocytes to overall PGE₂ production in the present system was minimal. On the basis of previous observations of PGE₂-associated inhibition of lymphocyte cytotoxicity against tumor cells in vitro, the present results suggest that tumor cell PGE₂ production may reflect a response of the tumor cells to challenge by effector lymphocytes and may represent a mechanism whereby tumor cells subvert an immune response mounted against them.