Stromal cells from human benign prostate hyperplasia produce a growth-inhibitory factor for LNCaP prostate cancer cells, identified as interleukin-6

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Abstract
To understand specific interactions between stromal cells and epithelial cells in benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma, we developed stromal‐cell cultures from normal human prostate (PNX) and BPH (BH101), composed of fibroblasts and myofibroblasts. Their role in epithelial‐cell growth was studied using the established cancer cell lines LNCaP, PC3 and DU 145 and an SV40 large T‐immortalized normal epithelial‐cell line, PNTIA, in double‐diffusion co‐culture chambers. PNTIA was stimulated by PNX (x 1.6) and more strongly by BH101 stromal cells (x 2.7). Conversely, LNCaP growth decreased by 50% in the presence of BH101 stromal cells (stromal/epithelial ratio: 10). A BH101‐conditioned medium (CM), obtained in serum‐free conditions, induced 90% inhibition of [3H]thymidine incorporation of the LNCaP androgen‐sensitive 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‐Iβ, 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 abolished this inhibition, which was reproduced by human recombinant IL‐6. Recombinant IL‐6 growth inhibition was observed only on LNCaP prostate cancer androgen‐sensitive cells. © 1996 Wiley‐Liss, Inc.

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