INTERACTION OF PROSTATE EPITHELIAL-CELLS FROM BENIGN AND MALIGNANT-TUMOR TISSUE WITH BONE-MARROW STROMA

BACKGROUND. Metastases of prostate cancer form selectively within the skeleton. To understand this metastatic spread, we studied the ability of prostate epithelial cells to grow and proliferate within the bone marrow, using primary coculture. METHODS. Prostate epithelia and fibro blasts were prepared from men with benign prostatic hyperplasia (n = 1 3) and cancer of the prostate (n = 10). Confluent cultures of bone-mar row stroma or fibroblast controls were prepared in 96-well plates, and identical plates were treated with detergent to expose the extracellu lar matrix of the cells. Epithelial cells were seeded onto either cell s or matrix, and their growth characteristics were determined by count ing increases in colony size and number over time. Further experiments evaluated the effects on epithelial growth when cells were exposed to media conditioned by these stroma, using an MTT assay. RESULTS. Resul ts showed that for epithelial cells derived from malignant (or benign) tissue, the median value of the total area of colonies formed on bone -marrow stroma was 2.1 (benign, 2.6) mm(2), in contrast to 0.3 (benign , 0.4) mm(2) or 0.25 (benign, 0) mm(2) when these cells were coculture d with fibroblasts from benign or malignant prostates, respectively. S tatistics indicated that growth was significantly greater on bone-marr ow stroma than on control stroma (P < 0.005). However, no significant stimulation of epithelial cell growth was seen when these epithelial c ells were cultured on extracellular matrix from bone-marrow stroma or when exposed to bone-marrow stroma-conditioned media in comparison to fibroblast controls. No statistical differences were found between the formation of colonies from malignant tissue in comparison to benign. CONCLUSIONS. This system allows the investigation of bone-marrow strom a colonization by primary prostate epithelial cells, and could be deve loped for the study of metastasis. (C) 1998 Wiley-Liss, Inc.