Production of prostaglandin E 2 by bladder tumor cells in tissue culture and a possible mechanism of lymphocyte inhibition

Abstract

Human bladder tumor cell lines were found to produce and secrete prostaglandin E 2 (PGE 2) in tissue culture and to be inhibited in this activity by prostaglandin synthetase inhibitors. The addition of purified peripheral blood lymphocytes from normal human donors to the tumor cells in confluent monolayers enhanced the production of PGE 2 by the tumor cells. At concentrations similar to those produced by the tumor cells, PGE 2 induced the intracellular accumulation of cyclic adenosine 3′, 5′-monophosphate by the lymphocytes. Both natural and antibody-dependent lymphocyte cytotoxicities by purified peripheral human blood lymphocytes directed against the same tumor target cells were inhibited by prostaglandins E 1 and E 2 and enhanced by the presence of indomethacin during incubation. Taken together, these phenomena suggest the possible existence of a mechanism whereby tumor cells, by the production of prostaglandins, may subvert the cellular immune response mounted against them and defend themselves from lymphocyte attack.