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Interleukin‐6 regulation of prostate cancer cell growth

Interleukin‐6 (IL‐6) is involved in regulation of immune reaction and cell growth and differentiation. It causes multifunctional responses ranging from inhibition of proliferation to promotion of cell survival. IL‐6 effects may depend on experimental conditions such as passage numbers and serum composition. IL‐6 signals in target tissues through the receptor that is composed of the ligand‐binding and signal‐transducing subunits. IL‐6 is expressed in benign and malignant prostate tissue and the levels of the cytokine and its receptor increase during prostate carcinogenesis. IL‐6 is considered a positive growth factor for most prostate cells. The only exemption seems to be the LNCaP cell line, in which IL‐6 causes growth arrest and induces differentiation function. In contrast, IL‐6 acts as an autocrine growth factor in the subline LNCaP‐IL‐6+ established after chronic treatment with IL‐6. IL‐6 is a candidate for targeted therapy in prostate cancer because of its association with morbidity. Activation of signaling pathways of Janus kinase/signal transducers and activators of transcription factors, mitogen‐activated protein kinase (MAPK), and phosphatidylinositol 3‐kinase has been reported in various prostate cancer cell lines. IL‐6 and the related cytokine oncostatin M induce activation of the androgen receptor (AR) in the absence of androgen. IL‐6 is also involved in regulation of vascular endothelial growth factor expression as well as neuroendocrine differentiation in prostate. Anti‐IL‐6 antibodies showed an inhibitory effect on the PC‐3 xenograft. However, the development of this therapy in prostate cancer is in early stages. © 2005 Wiley‐Liss, Inc.