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Depression: 21st Century Solutions + The Dark Side of Wheat

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.

Abstract:

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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Sayer Ji
Founder of GreenMedInfo.com

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Depression: 21st Century Solutions + The Dark Side of Wheat

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