Proliferative heterogeneity in the human prostate: Evidence for epithelialstem cells

Clonal analysis of human prostate epithelial cells was undertaken in order to identify stem cells. Two types of colony were distinguished, termed type I and type II. Type I colonies were relatively small and irregular and con tained a loose mixture of differentiated and undifferentiated cells. In con trast, type II colonies were large, round, and homogeneous, consisting almo st exclusively of small undifferentiated and dividing cells. The colony-for ming efficiency was 5.8% +/- 1.8 for freshly isolated epithelial cells. The re were approximately 10 times as many type I as type II colonies and about 1 in 200 of the plated cells was capable of forming a type II colony. In t hree-dimensional culture on Matrigel, the type II colonies produced structu res reminiscent of prostate epithelium, with luminal cells expressing marke rs of prostate epithelial differentiation, including the androgen receptor. On the basis of their proliferative characteristics and pluripotency, the type II colonies may be the progeny of stem cells and the type I colonies o f a more differentiated transit-amplifying population.