ROLE OF PROSTATIC BASAL CELLS IN THE REGULATION AND SUPPRESSION OF HUMAN PROSTATE-CANCER CELLS

Cytokeratin expression in normal and malignant prostatic tissue indica tes a loss of basal epithelial cells in cancer. We investigated the ab ility of basal-like prostatic epithelial cells to inhibit the growth o f prostatic cancer cells. Human prostate LNCaP cells were grown in med ium with or without 10 nM dihydrotestosterone (DHT) on plastic culture dishes or on extracellular matrix derived from basal-like epithelial cells (primary cultures derived from normal peripheral zone of the pro state) that were grown with or without 10 nM DHT. Calorimetric 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays we re used to assess the growth of LNCaP cells. On plastic dishes, growth of LNCaP cells was increased 5-10% by the presence of DHT in the medi um. On matrix derived from basal-like cells that were grown in the abs ence of DHT, growth of LNCaP cells with or without DHT was similar to that on plastic, However, on matrix derived from basal-like cells that were grown with DHT, growth of LNCaP cells was suppressed when compar ed to all other culture conditions (P < 0.01). To determine whether ba sal-like cells could alter the function of LNCaP cells, we measured pr ostate-specific antigen (PSA) mRNA expression with the use of comparat ive RT-PCR. We found a significant decrease in the mature PSA transcri pt in cells grown on matrix derived from basal-like cells that were gr own with DHT. The expression of PSA transcript was not altered in LNCa P cells that were grown on matrix derived from basal-like cells that w ere grown in the absence of DHT. Furthermore, using differential displ ay of mRNA, we demonstrated that there were induction and suppression of multiple unique transcripts in the LNCaP cells when grown on the va rious culture conditions. To determine a possible mechanism for these observations, we used a dot blot immunoassay for several known inhibit ory factors. We determined that DHT can induce the basal-like cells to secrete transforming growth factor-beta (TGF-beta 1), and that TGF-be ta 1 can inhibit the proliferation of LNCaP cells in a dose dependent manner. We conclude that basal-like epithelial cells, in the presence of DHT, secrete an extracellular matrix or matrix associated factor(s) , e.g. TGF-beta 1, that suppresses proliferation and function of prost ate cancer cells. Our data suggest that the disappearance of the basal cell layer may be a prerequisite for the progression of prostatic neo plasia.