ENHANCEMENT OF IN-VITRO PROSTAGLANDIN E(2) PRODUCTION BY MOUSE FIBROSARCOMA CELLS AFTER COCULTURE WITH VARIOUS ANTITUMOR EFFECTOR-CELLS

We have previously reported that an increase in the production of immunosuppressive prostaglandin E(2) by a QR tumour (QR-32) is accompanied by progressive growth of the tumour in syngeneic C57BL/6 mice. In order to determine what kinds of cell and factor(s) enable QR-32 cells to promote PGE(2) production, we investigated the amounts of PGE(2) in the supernatant of QR-32 cells by co-culturing them with various anti-tumour effector cells. Significantly high levels of PGE(2) production were observed when the QR-32 cells were co-cultured with lymphokine-activated killer (LAK) cells, natural killer (NK) cells, polymorphonuclear (PMN) leucocytes and streptococcal preparation (OK432)-activated or resident peritoneal macrophages (activated and resident macrophages). On the other hand, PGE(2) production was not increased when QR-32 cells were co-cultured with cytotoxic T lymphocytes (CTLs) specific to QR-32 cells. The high levels of PGE(2) production were partially or totally inhibited by the presence of radical scavengers such as superoxide dismutase (SOD), catalase and mannitol, although the cytotoxicity of LAK cells was not. We also exposed QR-32 cells to human recombinant cytokines and the growth factors which are produced when anti-tumour effector cells come in contact with tumour cells. Significant PGE(2) production by QR-32 cells was observed when the cells were treated with interferon alpha (IFN-alpha), tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) (all P <0.001). These results suggest that oxygen radicals produced by anti-tumour effector cells and inflammatory cytokines provoke QR-32 cells to produce large amounts of immunosuppressive PGE(2).