Inflammation and prostate cancer: the role of interleukin 6 (IL-6).
Environmental and genetic aspects are reflected in the development of prostate cancer. In this context, there is growing evidence that chronic inflammation is involved in the regulation of cellular events in prostate carcinogenesis, including disruption of the immune response and regulation of the tumour microenvironment. One of the best surrogates of chronic inflammation in prostate cancer is interleukin 6 (IL-6). Serum IL-6 levels are elevated in patients with untreated metastatic or castration-resistant prostate cancer (CRPC) and correlate negatively with tumour survival and response to chemotherapy. Via multiple signal pathways including the Janus tyrosine family kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, the extracellular signal-regulated kinase 1 and 2 (ERK1/2)-mitogen activated protein kinase (MAPK) pathway, and the phosphoinositide 3-kinase (PI3-K) pathway, IL-6 is able to promote prostate cancer cell proliferation and inhibit apoptosis in vitro and in vivo. IL-6 is associated with aggressive prostate cancer phenotype and may be involved in the metastatic process through regulation of epithelial-mesenchymal transition (EMT) and homing of cancer cells to the bone. A substantial body of evidence suggests that IL-6 plays a major role in the transition from hormone-dependent to CRPC, most notably through accessory activation of the androgen receptor. Collectively, these data have stimulated the development of agents targeting IL-6 signalling pathways. A chimeric anti-IL-6 monoclonal antibody has been tested in clinical trials, with mixed results.
Laboratory of Urological Oncology, Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, NY, USA; Department of Urology, University of Berne, Inselspital, Berne, Switzerland.
Daniel P
DP
Nguyen
Jinyi
J
Li
Ashutosh K
AK
Tewari
D006801:Humans; D007249:Inflammation / Q000276:immunology*; D015850:Interleukin-6 / Q000502:physiology*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology
D015850:Interleukin-6
androgen receptor; inflammation; interleukin-6; metastasis; prostate cancer; tumour growth