CELL-CELL INTERACTION IN PROSTATE GENE-REGULATION AND CYTODIFFERENTIATION

To examine the role of intercellular interaction on cell differentiati on and gene expression in human prostate, we separated the two major e pithelial cell populations and studied them in isolation and in combin ation with stromal cells, The epithelial cells were separated by flow cytometry using antibodies against differentially expressed cell-surfa ce markers CD44 and CD57, Basal epithelial cells express CD44, and lum inal epithelial cells express CD57. The CD57(+) luminal cells are the terminally differentiated secretory cells of the gland that synthesize prostate-specific antigen (PSA), Expression of PSA is regulated by an drogen, and PSA mRNA is one of the abundant messages in these cells, W e show that PSA expression by the CD57(+) cells is abolished after pro state tissue is dispersed by collagenase into single cells, Expression is restored when CD57(+) cells are reconstituted with stromal cells, The CD44(+) basal cells possess characteristics of stem cells and are the candidate progenitors of luminal cells, Differentiation, as reflec ted by PSA production, can be detected when CD44(+) cells are cocultur ed with stromal cells. Our studies show that cell-cell interaction pla ys an important role in prostatic cytodifferentiation and the maintena nce of the differentiated state.