INDUCTION OF TRANSFORMING GROWTH-FACTOR-BETA IN HORMONALLY TREATED HUMAN PROSTATE-CANCER

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 includ ing prostate, and in a recent study was shown to be up-regulated in th e stroma of breast cancer tissue following treatment with the anti-oes trogen tamoxifen. Immunolocalisation of the intracellular form of TGF- beta 1 confirmed that the source of the stromal TGF-beta 1 was the per itumoral fibroblasts. We present here the results of a study in which five patients with hormonally unresponsive prostatic carcinoma and sev en patients responding to a luteinising hormone-releasing hormone anal ogue had prostate biopsies taken before and during treatment. These we re stained for TGF-beta expression prior to treatment and at either re lapse or 3 months later respectively. Six of seven clinically respondi ng tumours and three of five relapsed tumours showed up-regulation of extracellular TGF-beta 1, again primarily in the stroma, with no appar ent 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.