Erythromyeloid tumor cells (K562) induce PGE synthesis in human peripheral blood monocytes.

Human peripheral blood monocytes were found to spontaneously produce prostaglandin of the E series (PGE) in culture medium (0.5 ng to 3.0 ng/7.5 X 10(5) cells), and the addition of K562 tumor cells enhanced the production by five- to 15-fold after 18 hr of incubation. PGE2 (10(-6) M) inhibited the cytolytic activity of freshly isolated peripheral blood monocytes against K562 target cells by 50%. The PGE production was inhibited by inhibitors of cyclo-oxygenase (indomethacin, aspirin, and ETYA) when present during the incubation. However, pretreatment of monocytes with these cyclo-oxygenase inhibitors was ineffective in preventing PGE production. Kinetic experiments showed that appreciable stimulation of PGE production occurred only after 6 hr of co-culture. Other human tumor cell lines (HSB, SB, and CEM) enhanced PGE production upon co-culture with monocytes but to a lesser extent (twofold to threefold). Monocytes treated with 0.4% formaldehyde or heat (56 degrees C) were not capable of producing PGE when cultured alone or with K526 tumor cells. In contrast, formaldehyde-treated, but not heat-treated, K562 tumor cells were able to induce monocytes to produce PGE. By using a single cell conjugation assay, K562 tumor cells were found to bind equally well to treated or untreated monocytes. In contrast, the lytic activity of treated monocytes against K562 target cells was abolished. The presence of protein synthesis inhibitor, cycloheximide, was found to inhibit PGE production by monocytes cultured alone or with K562 tumor cells. Supernatants from K562 tumor cell cultures were also capable of inducing monocytes to produce PGE, and their effect on PGE production from monocytes was suppressed by cycloheximide. In addition, pretreatment of either K562 tumor cells or monocytes with an irreversible protein synthesis inhibitor, emetine, also suppressed the production of PGE upon co-culture with the untreated counterpart. The production of PGE by monocytes in response to exposure to tumor cells may represent a mechanism whereby tumor cells subvert host immune defense against them.