Induction of transforming growth factor beta in hormonally treated human prostate cancer

Br J Cancer. 1994 Jan;69(1):130-4. doi: 10.1038/bjc.1994.21.

Abstract

Transforming growth factor beta-1 (TGF-beta 1) has been proposed as a mediator of tumour growth in a number of tumours and cell lines including prostate, and in a recent study was shown to be up-regulated in the stroma of breast cancer tissue following treatment with the anti-oestrogen tamoxifen. Immunolocalisation of the intracellular form of TGF-beta 1 confirmed that the source of the stromal TGF-beta 1 was the peritumoral fibroblasts. We present here the results of a study in which five patients with hormonally unresponsive prostatic carcinoma and seven patients responding to a luteinising hormone-releasing hormone analogue had prostate biopsies taken before and during treatment. These were stained for TGF-beta expression prior to treatment and at either relapse or 3 months later respectively. Six of seven clinically responding tumours and three of five relapsed tumours showed up-regulation of extracellular TGF-beta 1, again primarily in the stroma, with no apparent up-regulation of intracellular TGF-beta 1, TGF-beta 2 or TGF-beta 3. These data illustrate that the epithelial growth inhibitor TGF-beta 1 can be induced by hormonal manipulation in prostate cancer in vivo, and may continue to be up-regulated even after relapse. This suggests that relapse of hormonally treated prostate cancer may be associated with a failure of the epithelium to respond to stromal TGF-beta 1.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androgens / pharmacology
  • Biopsy
  • Diethylstilbestrol / therapeutic use*
  • Extracellular Space / metabolism
  • Humans
  • Immunohistochemistry
  • Leuprolide / therapeutic use*
  • Male
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / metabolism
  • Orchiectomy
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Androgens
  • Transforming Growth Factor beta
  • Diethylstilbestrol
  • Leuprolide