TGF-beta signalling and immunity in prostate tumourigenesis.

ABSTRACT

IMPORTANCE OF THE FIELD The TGF-beta's are pleiotropic cytokines that regulate multiple cellular functions. Their role in the prostate is important for normal prostate development and also in prostate tumourigenesis. AREAS COVERED IN THIS REVIEW The interactions TGF-beta-mediated signalling has with maintaining prostate health, as well as its role in prostate tumourigenesis and prostate tumour immune evasion, with emphasis on how a breakdown in these interactions may influence disease progression. WHAT THE READER WILL GAIN That TGF-beta influences normal prostate growth and differentiation by regulating the balance between epithelial cell proliferation and apoptosis, and involving the androgen receptor pathway. That TGF-beta protects and maintains prostate stem cells and a review of the contrasting role TGF-beta has in prostate tumourigenesis and tumour development, where TGF-beta acts as a tumour suppressor and then switches roles to become a tumour promoter, and creates a local immunosuppressive niche leading to systemic tumour tolerance. TAKE HOME MESSAGE TGF-beta signalling in prostate cancer is a valid target for the treatment of this disease; however any therapeutic regimen will require an understanding of all aspects of the TGF-beta-signalling nexus, otherwise by the very pleiotrophic nature of TGF-beta, limited clinical benefits may result.