Interleukin-6 (IL-6), a pleiotropic regulator of prostate cancer cell proliferation and apoptosis, and oncostatin M (OSM), an IL-6-type cytokine, affect the growth of prostate cancers in a paracrine and autocrine manner. In order to understand better the mechanisms controling proliferation and intracellular signaling by these cytokines in advanced prostate carcinoma, we performed studies in 22Rv1 cells derived from the relapsed xenograft CWR22R. Expression of IL-6 and OSM receptors and elements of signal transduction pathways in 22Rv1 cells were investigated by RT-PCR. IL-6 secretion was measured in conditioned medium from 22Rv1 cells by ELISA. Expression and phosphorylation of signal transducers and activators of transcription factor (STAT) 3, mitogen-activated protein kinases p44/p42 and p38, and Akt was investigated by Western blot. 22Rv1 cells express both subunits of the IL-6 receptor (gp80 and gp130) and leukemia inhibitory factor receptor-β but not OSM receptor-β. IL-6 was not detectable in conditioned medium from 22Rv1 cells. Their proliferation was stimulated by exogenous IL-6 or OSM and the maximal effect was observed at a concentration of 10 ng/ml of either cytokine. Neither IL-6 nor OSM induced phosphorylation of STAT3 or p44/p42 kinases. Both cytokines increased Akt phosphorylation. In addition, OSM showed a modest stimulatory effect on p38 phosphorylation. IL-6 and OSM stimulate proliferation of 22Rv1 cells, at least in part through activation of the phosphatidylinositol 3-kinase signaling pathway. Our data provide additional evidence for the growth-stimulatory role of IL-6 and related cytokines in advanced prostate cancer and may serve as a basis for the development of novel experimental therapies.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]