Interleukin-6 Function and Targeting in Prostate Cancer.

Abstract

Interleukin-6 (IL-6) is a proinflammatory cytokine, which is involved in pathogenesis of several cancers. Its expression and function in prostate cancer have been extensively studied in cellular models and clinical specimens. High levels of IL-6 were detected in conditioned media from cells which do not respond to androgens. Increased phosphorylation of signal transducer and activator of transcription (STAT)3 factor which is induced in response to IL-6 is one of the typical features of prostate cancer. However, reports in the literature show regulation of neuroendocrine phenotype by IL-6. Effects of IL-6 on stimulation of proliferation, migration, and invasion lead to the establishment of experimental and clinical approaches to target IL-6. In prostate cancer, anti-IL-6 antibodies were demonstrated to inhibit growth in vitro and in vivo. Clinically, application of anti-IL-6 therapies did not improve survival of patients with metastatic prostate cancer. However, clinical trial design in the future may include different treatment schedule and combinations with experimental and clinical therapies. Endogenous inhibitors of IL-6 such as suppressors of cytokine signaling and protein inhibitors of activated STAT have variable effects on prostate cells, depending on presence or absence of the androgen receptor.