Interleukin-6 induces prostate cancer cell growth accompanied by activation of Stat3 signaling pathway

BACKGROUND Interleukin‐6 (IL‐6) is a pleiotropic cytokine that regulates growth and differentiation of various types of malignant tumors, including prostate carcinomas. The levels of IL‐6 are elevated in sera of patients with metastatic prostate cancer. In this study, we evaluate the role of IL‐6 in the growth regulation of prostate cancer cells. METHODS Expression of IL‐6 and its receptors in human prostate cancer cells was measured by ELISA and RT‐PCR. The effects of IL‐6 on cell growth were evaluated by ectopically expressing IL‐6 cDNA into IL‐6‐negative LNCaP human prostate cancer cells. Stat3 DNA binding activities were analyzed by electromobility shift assay and supershift assay. RESULTS Expression of IL‐6 was detected in the androgen‐insensitive prostate cancer cell lines (i.e., TSU, PC3, and DU145), but not in the androgen‐sensitive LNCaP cell line. IL‐6 receptors, including both IL‐6‐specific receptor α chain and gp130 signal transducer, are expressed in all human prostate cancer cell lines (i.e., LNCaP, TSU, PC3, and DU145). Overexpression of IL‐6 by ectopically expressing IL‐6 into IL‐6‐negative LNCaP human prostate cancer cells significantly increased clonogenic ability and cell proliferation in vitro compared to the IL‐6‐negative parental LNCaP cells and the antisense controls. This growth stimulation by IL‐6 was accompanied by activation of the Stat3 signaling transduction pathway. CONCLUSIONS IL‐6 is an autocrine growth factor for LNCaP human prostate cancer cells; the effects of IL‐6 on prostate cancer cell growth are mediated through the Janus kinase‐signal transducers and activators of transcription (JAK‐STAT) signaling pathway. Prostate 42:239–242, 2000. © 2000 Wiley‐Liss, Inc.