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.