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 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.
Muir
G H
GH
Urology Unit, Institute of Cancer Research, London, UK.
Butta
A
A
Shearer
R J
RJ
Fisher
C
C
Dearnaley
D P
DP
Flanders
K C
KC
Sporn
M B
MB
Colletta
A A
AA
D000728:Androgens / Q000494:pharmacology; D001706:Biopsy; D004054:Diethylstilbestrol / Q000627:therapeutic use*; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016729:Leuprolide / Q000627:therapeutic use*; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000728:Androgens; D016212:Transforming Growth Factor beta; D004054:Diethylstilbestrol; D016729:Leuprolide