Interleukin-6 regulation of prostate cancer cell growth
Article first published online: 18 APR 2005
Copyright © 2005 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 95, Issue 3, pages 497–505, 1 June 2005
How to Cite
Culig, Z., Steiner, H., Bartsch, G. and Hobisch, A. (2005), Interleukin-6 regulation of prostate cancer cell growth. J. Cell. Biochem., 95: 497–505. doi: 10.1002/jcb.20477
- Issue published online: 10 MAY 2005
- Article first published online: 18 APR 2005
- Manuscript Accepted: 11 FEB 2005
- Manuscript Received: 10 FEB 2005
- prostate cancer;
- androgen receptor
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.