Intermediate basal cells of the prostate: in vitro and in vivo characterization.
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.
Garraway
Levi A
LA
Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Lin
Douglas
D
Signoretti
Sabina
S
Waltregny
David
D
Dilks
James
J
Bhattacharya
Nandita
N
Loda
Massimo
M
D015153:Blotting, Western; D002454:Cell Differentiation; D016922:Cellular Senescence / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011498:Protein Precursors / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D011498:Protein Precursors; D011944:Receptors, Androgen; C032253:involucrin; D012313:RNA; D007633:Keratins