%0 Journal Article
%T Epcam, CD44, and CD49f Distinguish Sphere-Forming Human Prostate Basal Cells from a Subpopulation with Predominant Tubule Initiation Capability
%A Changyong Guo
%A Haibo Liu
%A Bao-Hui Zhang
%A Radu M. Cadaneanu
%A Aqila M. Mayle
%A Isla P. Garraway
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0034219
%X Background Human prostate basal cells expressing alpha-6 integrin (CD49fHi) and/or CD44 form prostaspheres in vitro. This functional trait is often correlated with stem/progenitor (S/P) activity, including the ability to self-renew and induce differentiated tubules in vivo. Antigenic profiles that distinguish tubule-initiating prostate stem cells (SCs) from progenitor cells (PCs) and mature luminal cells (LCs) with less regenerative potential are unknown. Methodology/Principle Findings Prostasphere assays and RT-PCR analysis was performed following FACS separation of total benign prostate cells based upon combinations of Epcam, CD44, and/or CD49f expression. Epithelial cell fractions were isolated, including Epcam+CD44+ and Epcam+CD44+CD49fHi basal cells that formed abundant spheres. When non-sphere-forming Epcam+CD44£¿ cells were fractionated based upon CD49f expression, a distinct subpopulation (Epcam+CD44£¿CD49fHi) was identified that possessed a basal profile similar to Epcam+CD44+CD49fHi sphere-forming cells (p63+ARLoPSA£¿). Evaluation of tubule induction capability of fractionated cells was performed, in vivo, via a fully humanized prostate tissue regeneration assay. Non-sphere-forming Epcam+CD44£¿ cells induced significantly more prostate tubular structures than Epcam+CD44+ sphere-forming cells. Further fractionation based upon CD49f co-expression identified Epcam+CD44£¿CD49fHi (non-sphere-forming) basal cells with significantly increased tubule induction activity compared to Epcam+CD44£¿CD49fLo (true) luminal cells. Conclusions/Significance Our data delineates antigenic profiles that functionally distinguish human prostate epithelial subpopulations, including putative SCs that display superior tubule initiation capability and induce differentiated ductal/acini structures, sphere-forming PCs with relatively decreased tubule initiation activity, and terminally differentiated LCs that lack both sphere¨Cforming and tubule-initiation activity. The results clearly demonstrate that sphere-forming ability is not predictive of tubule-initiation activity. The subpopulations identified are of interest because they may play distinct roles as cells of origin in the development of prostatic diseases, including cancer.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0034219