STROMAL CELLS FROM HUMAN BENIGN PROSTATE HYPERPLASIA PRODUCE A GROWTH-INHIBITORY FACTOR FOR LNCAP PROSTATE-CANCER CELLS, IDENTIFIED AS INTERLEUKIN-6

To understand specific interactions between stromal cells and epitheli al cells in benign prostatic hyperplasia (BPH) and prostatic adenocarc inoma, we developed stromal-cell cultures from normal human prostate ( PNX) and BPH (BH101), composed of fibroblasts and myofibroblasts. Thei r role in epithelial-cell growth was studied using the established can cer cell lines LNCaP, PC3 and DU145 and an SV40 large T-immortalized n ormal epithelial-cell line, PNTIA, in double-diffusion co-culture cham bers. PNTIA was stimulated by PNX (x1.6) and more strongly by BH101 st romal cells (x2.7). Conversely, LNCaP growth decreased by 50% in the p resence of BH101 stromal cells (stromal/epithelial ratio: 10). A BH101 -conditioned medium (CM), obtained in serum-free conditions, induced 9 0% inhibition of [H-3]thymidine incorporation of the LNCaP androgen-se nsitive cell line. Two other androgen-independent prostate cancer cell lines were either insensitive to BH101 CM (PC3) or slightly inhibited (40% for DU145). BH101 produced large amounts of IL-1 beta, IL-6 and IL-8. HPLC gel filtration enabled separation of an inhibitory fraction which contained IL-6. IL-6 was demonstrated to be responsible for the strong inhibitory effect since an IL-6-neutralizing antibody abolishe d this inhibition, which was reproduced by human recombinant IL-6. Rec ombinant IL-6 growth inhibition was observed only on LNCaP prostate ca ncer androgen-sensitive cells. (C) 1996 Wiley-Liss, Inc.