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

Abstract

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. 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. 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 alpha 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. 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.