Foley, C.L.; (2007) Characterisation of human prostate epithelium colony forming cells. Doctoral thesis , University of London.

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Abstract

Objectives: Rare prostate epithelial stem cells have been implicated in the aetiology of prostate disease, yet are overlooked in studies on the whole tissue. When prostate epithelial cells are cultured at low density, two distinct colony types arise, postulated to represent the progeny of stem cells (type II colonies) and committed 'transit amplifying' cells (type I). This project aimed to further characterize these rare colonies and confirm their position in the prostate epithelial cell hierarchy, in benign, and for the first time, malignant tissue. Methods: Colonies derived from transurethral resection tissue were compared for proliferation, differentiation, colony self-renewal and gene expression. Paired benign and malignant radical prostatectomy samples were cultured. To confirm the benign / malignant nature of individual colonies, loss of heterozygosity and expression of known prostate cancer markers were assessed. Results: There was a trend to greater type II colony proliferation, but no difference in ability to differentiate into multi-layered acinus-like structures expressing early and late epithelial markers. When passaged, type II colonies never re-created themselves, but resembled type I colonies. Using cDNA microarrays, comparison of gene expression in the two colony types showed a limited magnitude of differences, most notably in differentiation markers. Malignant tissue yielded both colony types, which were indistinguishable from their benign counterparts. Neither loss of heterozygosity analysis nor prostate cancer marker expression distinguished benign from malignant colonies. Conclusions: These colonies behave like differently-aged populations of transit amplifying cells - the committed offspring of the stem cell. If a stem cell does generate type II colonies, it appears to lose self-renewal ability and differentiate in culture. Colonies derived from cancer tissue show neither a malignant genotype nor phenotype suggesting that malignant cells are not cultured in these conditions. This highlights the need to confirm malignancy in primary prostate cancer cultures, hitherto assumed by many authors.

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