Abstract Title:

Stem-Like Cells with Luminal Progenitor Phenotype Survive Castration in Human Prostate Cancer.

Abstract Source:

Stem Cells. 2012 Mar 21. Epub 2012 Mar 21. PMID: 22438320

Abstract Author(s):

Markus Germann, Antoinette Wetterwald, Natalia Guzmán-Ramirez, Gabri van der Pluijm, Zoran Culig, Marco G Cecchini, Elizabeth D Williams, George N Thalmann

Article Affiliation:

Urology Research Laboratory, Department of Urology and Department of Clinical Research, University of Bern, Bern, Switzerland.


Castration is the standard therapy for advanced prostate cancer (PC). Although this treatment is initially effective, tumors invariably relapse as incurable, castration-resistant PC (CRPC). Adaptation of androgen-dependent PC cells to an androgen-depleted environment or selection of pre-existing, CRPC cells have been proposed as mechanisms of CRPC development. Stem cell (SC)-like PC cells have been implicated not only as tumor initiating/maintaining in PC, but also as tumor re-initiating cells in CRPC. Recently, CRPC cells, named CARNs, expressing the luminal markers NK3 homeobox 1 (Nkx3-1), cytokeratin 18 (CK18) and androgen receptor (AR), and possessing SC properties, have been found in castrated mice and proposed as the cell-of-origin of CRPC. However, the human counterpart of CARNs has not been identified yet. Here we demonstrate that in the human PC xenograft BM18 pre-existing stem cell (SC)-like and neuroendocrine (NE) PC cells are selected by castration and survive as totally quiescent. SC-like BM18 cells, displaying the SC markers aldehyde dehydrogenase 1A1 (ALDH1A1) or NANOG, co-express the luminal markers NKX3-1, CK18, and a low level of AR (AR(low) ), but not basal or NE markers. These CR luminal SC-like cells, but not NE cells, re-initiate BM18 tumor growth after androgen-replacement. The AR(low) seems to mediate directly both castration survival and tumor re-initiation. This study identifies for the first time in human PC SC-/CARN-like cells that may represent the cell-of-origin of tumor re-initiation as CRPC. This finding will be fundamental for refining the hierarchy among human PC cancer cells and may have important clinical implications.

Study Type : In Vitro Study

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