TGF-beta signalling and immunity in prostate tumourigenesis

Expert Opin Ther Targets. 2010 Feb;14(2):179-92. doi: 10.1517/14728220903544507.

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.

Publication types

  • Review

MeSH terms

  • Androgen Antagonists / pharmacology
  • Animals
  • Humans
  • Lymphocyte Activation
  • Male
  • Prostatic Neoplasms / etiology*
  • Prostatic Neoplasms / immunology*
  • Proteoglycans / physiology
  • Receptors, Androgen / physiology
  • Receptors, Transforming Growth Factor beta / physiology
  • Signal Transduction / physiology*
  • Stem Cells / physiology
  • T-Lymphocytes / immunology
  • Transforming Growth Factor beta / physiology*
  • Tumor Escape

Substances

  • Androgen Antagonists
  • Proteoglycans
  • Receptors, Androgen
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • betaglycan