Intermediate basal cells of the prostate: in vitro and in vivo characterization.

TitleIntermediate basal cells of the prostate: in vitro and in vivo characterization.
Publication TypeJournal Article
Year of Publication2003
AuthorsGarraway LA, Lin D, Signoretti S, Waltregny D, Dilks J, Bhattacharya N, Loda M
JournalProstate
Volume55
Issue3
Pagination206-18
Date Published2003 May 15
ISSN0270-4137
KeywordsBlotting, Western, Cell Differentiation, Cellular Senescence, Epithelial Cells, Humans, Immunohistochemistry, Keratins, Male, Prostate, Prostatic Neoplasms, Protein Precursors, Receptors, Androgen, Reverse Transcriptase Polymerase Chain Reaction, RNA, Stem Cells
Abstract

BACKGROUND: Progenitor cells within the prostate basal layer may play important roles in differentiation and carcinogenesis; however, prostate stem cell populations remain uncharacterized.

METHODS: Immunohistochemical and immunoblot analyses were used to characterize prostate epithelial cells (PrEC), a commercially available prostate basal cell isolate.

RESULTS: Proliferating PrECs exhibited immunophenotypic characteristics most consistent with basal cells, but during senescence PrECs up-regulated androgen receptor (AR) mRNA, p27, and low-molecular-weight cytokeratin (LMWCK) expression, suggestive of partial differentiation. PrECs also stained strongly for involucrin, which marked a subset of intermediate prostate basal cells in vivo. Basal hyperplasia consisting of involucrin-positive cells was prevalent in prostate tissue from androgen-ablated patients, and formed epithelial clusters flanked by involucrin-negative basal and luminal monolayers. Cultivation of PrECs on matrigel together with androgen-treated stromal conditioned media resulted in dense aggregates, with a peripheral rim of basal-like cells expressing p63 and basal cytokeratins.

CONCLUSIONS: PrEC represents an epithelial population whose basal characteristics are modified in response to matrigel, stromal factors, and senescence, consistent with a transient amplifying population. These cells may derive from a previously unrecognized, involucrin-positive subset present in vivo.

DOI10.1002/pros.10244
Alternate JournalProstate
PubMed ID12692787
Grant ListR01-CA81755 / CA / NCI NIH HHS / United States
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Massimo Loda, M.D.

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