Epcam, CD44, and CD49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability.

<h4>Background</h4>Human prostate basal cells expressing alpha-6 integrin (CD49f(Hi)) 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. Ant...

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Autores principales:	Changyong Guo, Haibo Liu, Bao-Hui Zhang, Radu M Cadaneanu, Aqila M Mayle, Isla P Garraway
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70e32c3fcf324e7f9be8078ed8d41c10
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spelling	oai:doaj.org-article:70e32c3fcf324e7f9be8078ed8d41c102021-11-18T07:22:20ZEpcam, CD44, and CD49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability.1932-620310.1371/journal.pone.0034219https://doaj.org/article/70e32c3fcf324e7f9be8078ed8d41c102012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22514625/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Human prostate basal cells expressing alpha-6 integrin (CD49f(Hi)) 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.<h4>Methodology/principle findings</h4>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+CD49f(Hi) basal cells that formed abundant spheres. When non-sphere-forming Epcam(+)CD44(-) cells were fractionated based upon CD49f expression, a distinct subpopulation (Epcam(+)CD44(-)CD49f(Hi)) was identified that possessed a basal profile similar to Epcam(+)CD44(+)CD49f(Hi) sphere-forming cells (p63(+)AR(Lo)PSA(-)). 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(-)CD49f(Hi) (non-sphere-forming) basal cells with significantly increased tubule induction activity compared to Epcam(+)CD44(-)CD49f(Lo) (true) luminal cells.<h4>Conclusions/significance</h4>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-forming 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.Changyong GuoHaibo LiuBao-Hui ZhangRadu M CadaneanuAqila M MayleIsla P GarrawayPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34219 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Changyong Guo Haibo Liu Bao-Hui Zhang Radu M Cadaneanu Aqila M Mayle Isla P Garraway Epcam, CD44, and CD49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability.
description	<h4>Background</h4>Human prostate basal cells expressing alpha-6 integrin (CD49f(Hi)) 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.<h4>Methodology/principle findings</h4>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+CD49f(Hi) basal cells that formed abundant spheres. When non-sphere-forming Epcam(+)CD44(-) cells were fractionated based upon CD49f expression, a distinct subpopulation (Epcam(+)CD44(-)CD49f(Hi)) was identified that possessed a basal profile similar to Epcam(+)CD44(+)CD49f(Hi) sphere-forming cells (p63(+)AR(Lo)PSA(-)). 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(-)CD49f(Hi) (non-sphere-forming) basal cells with significantly increased tubule induction activity compared to Epcam(+)CD44(-)CD49f(Lo) (true) luminal cells.<h4>Conclusions/significance</h4>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-forming 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.
format	article
author	Changyong Guo Haibo Liu Bao-Hui Zhang Radu M Cadaneanu Aqila M Mayle Isla P Garraway
author_facet	Changyong Guo Haibo Liu Bao-Hui Zhang Radu M Cadaneanu Aqila M Mayle Isla P Garraway
author_sort	Changyong Guo
title	Epcam, CD44, and CD49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability.
title_short	Epcam, CD44, and CD49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability.
title_full	Epcam, CD44, and CD49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability.
title_fullStr	Epcam, CD44, and CD49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability.
title_full_unstemmed	Epcam, CD44, and CD49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability.
title_sort	epcam, cd44, and cd49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/70e32c3fcf324e7f9be8078ed8d41c10
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Epcam, CD44, and CD49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability.

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