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 degrees, 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.