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 g rowth and differentiation of various types of malignant tumors, including p rostate carcinomas. The levels of IL-6 are elevated in sera of patients wit h metastatic prostate cancer. Ln this study, we evaluate the role of IL-6 i n the growth regulation of prostate cancer cells. METHODS. Expression of IL-6 and its receptors in human prostate cancer cell s 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 hum an prostate cancer cells. Stat3 DNA binding activities were analyzed by ele ctromobility shift assay and supershift assay. RESULTS. Expression of IL-6 was detected in the androgen-insensitive prosta te cancer cell lines (i.e., TSU, PC3, and DU145), but not in the androgen-s ensitive LNCaP cell line. IL-6 receptors, including both IL-6-specific rece ptor alpha chain and gp130 signal transducer, are expressed in all human pr ostate 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 pros tate cancer cells significantly increased clonogenic ability and cell proli feration in vitro compared to the IL-6-negative parental LNCaP cells and th e antisense controls. This growth stimulation by IL-6 was accompanied by ac tivation of the Stat3 signaling transduction pathway. CONCLUSIONS. IL-6 is an autocrine growth factor for LNCaP human prostate ca ncer cells; the effects of IL-6 on prostate cancer cell growth are mediated through the Janus kinase-signal transducers and activators of transcriptio n (JAK-STAT) signaling pathway. (C) 2000 Wiley-Liss, Inc.