INTERLEUKIN-1-BETA MEDIATES THE MODULATORY EFFECTS OF MONOCYTES ON LNCAP HUMAN PROSTATE-CANCER CELLS

Proliferative and secretory responses in androgen-sensitive prostate c ancer LNCaP cells are regulated by steroid and peptide hormones and by differentiation-promoting substances. In the present study, we evalua ted whether peripheral blood monocytes that exhibit anti-tumour activi ty in haematopoietic and solid tumours influence growth and secretion in the LNCaP cell line. For this purpose, LNCaP cells were incubated w ith monocyte-conditioned medium (MCM), and proliferation as well as ex pression of androgen receptor (AR) and secretion of prostate-specific antigen (PSA) were assessed. Conditioned medium from monocytes reduced proliferation in a dose-dependent manner. Incubation with 40% MCM cau sed a 50% reduction in cell proliferation. AR protein decreased by 70% and PSA levels in supernatants from LNCaP cells were reduced by appro ximately 80% following treatment with MCM. We focused on the contribut ion of two major products of activated monocytes, prostaglandin E-2 an d interleukin 1 beta (IL-1 beta), to the MCM modulatory action. LNCaP cells treated with prostaglandin E-2 showed neither a reduction in pro liferation nor a down-regulation of AR and PSA levels. The effects of MCM on cellular proliferation, AR protein and PSA secretion were aboli shed by pretreatment of MCM with a neutralizing anti-IL-1 beta antibod y, In addition, recombinant IL-1 beta was able to replace MCM for the inhibition of proliferation and down-regulation of AR and PSA proteins . LNCaP cells were shown to express the IL-1 beta receptor type I, whi ch transduces IL-1 beta signal. Our findings reveal that monocyte-deri ved IL-1 beta inhibits the proliferation of androgen-responsive prosta te tumour cells and reduces AR and PSA levels.