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 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 DU145 and an SV40 large T-immortalized normal epithelial-cell line, PNT1A, in double-diffusion co-culture chambers. PNT1A was stimulated by PNX (x1.6) and more strongly by BH101 stromal cells (x2.7). 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-1beta, 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.
Laboratoire de Pharmacologie, Institut de Génétique Moléculaire, Hôpital Saint-Louis, Paris, France.
A
A
Degeorges
R
R
Tatoud
F
F
Fauvel-Lafeve
M P
MP
Podgorniak
G
G
Millot
P
P
de Cremoux
F
F
Calvo
D000328:Adult; D002450:Cell Communication; D002455:Cell Division; D002851:Chromatography, High Pressure Liquid; D018920:Coculture Techniques; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000187:drug effects; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D006131:Growth Inhibitors; D015850:Interleukin-6