Basal Progenitors Contribute to Repair of the Prostate Epithelium Following Induced Luminal Anoikis.
Contact with the extracellular matrix is essential for maintenance of epithelial cells in many tissues, while in its absence epithelial cells can detach and undergo anoikis. Here, we show that anoikis of luminal cells in the prostate epithelium is followed by a program of tissue repair that is mediated in part by differentiation of basal epithelial cells to luminal cells. We describe a mouse model in which inducible deletion of E-cadherin in prostate luminal cells results in their apoptotic cell death by anoikis, in the absence of phenotypic effects in the surrounding stroma. Quantitative assessments of proliferation and cell death in the luminal and basal compartments indicate that basal cells can rapidly generate luminal cells. Thus, our findings identify a role for basal-to-luminal differentiation in prostate epithelial repair, and provide a normal context to analogous processes that may occur during prostate cancer initiation.
Departments of Medicine, Genetics & Development, Urology, and Systems Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
Roxanne
R
Toivanen
Departments of Medicine, Genetics & Development, Urology, and Systems Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
Adithi
A
Mohan
Departments of Medicine, Genetics & Development, Urology, and Systems Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: mshen@columbia.edu.
Michael M
MM
Shen
D000818:Animals; D023102:Anoikis / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D011467:Prostate / Q000254:growth & development / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism
D015820:Cadherins
anoikis; epithelial lineage; prostate; stem cells; tissue repair