Characterization of the role of IL-6 in the progression of prostate cancer

BACKGROUND. We recently identified IL-6, a pleiotropic cytokine implicated in the neo-plastic process of a variety of neoplasms, as a mediator of pros tate cancer morbidity. In the present study, we investigated the expression of members of the IL-6 supergene family and related cytokines and the pote ntial role of IL-6 in prostate cancer growth regulation. METHODS. Five established human prostate cancer cell lines were screened by ELISA for production of granulocyte colony-stimulating factor (G-CSF), leu kemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostat in M (OSM), tumor necrosis factor (TNF), interleukin-l (IL-1), and granuloc yte macrophage colony-stimulating factor (GM-CSF). Expression of the Ligand -binding component of the IL-6 receptor, IL-6Rp80, was evaluated by ELISA a nd RT-PCR. Sequential immunoprecipitation and immunoblotting were performed to assay for expression of the signal-transducing component of the IL-6 re ceptor, gp130. The effects of IL-6 on cell growth were assessed by MTT assa ys. RESULTS. The three hormone-refractory cell lines, DU-145, TSU, and PC-3, se creted distinct combinations of cytokines (DU-145: IL-6, GM-CSF; TSU: IL-6, LIF; PC-3: IL-6, G-CSF, LIF, IL-1, GM-CSF), each uniformly expressing IL-6 . Ln contrast, neither of the two hormone-dependent cell lines, LNCaP-ATCC and LNCaP-GW, secreted significant quantities of any of the cytokines analy zed. None of the cell lines secreted detectable quantities of OSM, CNTF, or TNF. All cell lines, irrespective of hormone status, expressed both Il-6Rp 80 and gp130. Addition of IL-6 in vitro inhibited growth of hormone-depende nt cells, but had no effect on hormone-refractory lines. Anti-IL-6 neutrali zing antibody inhibited growth of hormone-refractory cells. CONCLUSIONS. IL-6 appears to undergo a functional transition from paracrine growth inhibitor to autocrine growth stimulator during progression of pros tate cancer to the hormone-refractory phenotype. (C) 1999 Wiley-Liss, Inc.