Epithelial cell differentiation in the human prostate epithelium: Implications for the pathogenesis and therapy of prostate cancer

Within the human prostate epithelium four cell populations are discriminated by their expression of keratins (K). While basal cells co-localize K5 and K14 combined with low levels of K18 (K5(+ +) /14(+ +)/18(+)), luminal cells highly express K18 (K18(+ +)). In addition, two intermediate subpopulations are characterized either by basal K5(+ +)/18(+) - or luminal K5(+)/18(+ +) - expression. The entire prostate epithelium is putatively derived from a basal stem cell population. They give rise to intermediate cells that transiently proliferate and mature towards differentiated luminal epithelium. Within prostate carcinoma luminal exocrine, neuro-endocrine and intermediate cells are distinguished. Intermediate cells have been postulated as progenitors for prostate carcinogenesis and targets for androgen-independent tumor progression. Androgen-independency is associated with an enrichment of intermediate cells and over-expression of peptide growth factor receptors. Targeting intermediate cells by inhibition of their peptide growth factor receptors, therefore, offers novel treatment modalities for prostate cancer. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.