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Evidence of pluripotent human prostate stem cells in a human prostate primary xenograft model
Author(s) -
Huss Wendy J.,
Gray Danny R.,
Werdin Eric S.,
Funkhouser William K.,
Smith Gary J.
Publication year - 2004
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20041
Subject(s) - stem cell , prostate , prostate cancer , population , biology , androgen , transplantation , testosterone (patch) , cancer research , endocrinology , pathology , medicine , microbiology and biotechnology , cancer , hormone , environmental health
Abstract INTRODUCTION The phenotypic plasticity of the human prostate stem cell within human prostate tissue was examined to determine the response of the stem cell to changes in the androgenic environment. METHODS Prostate xenografts were transplanted into athymic nu / nu mice implanted with testosterone pellets, allowed to establish for 1 month time point, the hosts were castrated and pellets removed, and following 1 month of androgen deprivation, the hosts were stimulated with androgen for 2 days to induce proliferation of the residual population of stem cells (2‐month time point). RESULTS Glands in benign xenografts harvested at the 1‐ and 2‐month time points contained basal cell layers that expressed p63 and high molecular weight cytokeratin, and in which essentially all of the cellular proliferation was localized, consistent with the proposed localization of the prostate stem cell. Benign glandular structures in the xenografts were populated by basal, secretory epithelial, neuroendocrine (NE), or squamous cells overlaying the basal cell layer, whereas, adenocarcinoma glands in the xenografts resembled the original prostate cancer (CaP) tissue. CONCLUSIONS In this human prostate primary xenograft model, the residual stem cell population that survives transplantation, or androgen deprivation, maintains significant pluripotentiality as demonstrated by the capacity to generate progeny that differentiate along multiple lineages in response to microenvironmental signals, particularly along the secretory epithelial lineage in response to androgen, and along the NE cell lineage in response to androgen deprivation. © 2004 Wiley‐Liss, Inc.