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

被引:78
作者
Garraway, LA
Lin, D
Signoretti, S
Waltregny, D
Dilks, J
Bhattacharya, N
Loda, M
机构
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA
[3] Univ Liege, Univ Hosp, Metastasis Res Lab, Liege, Belgium
关键词
prostate; PrEC; stem cells; p63; differentiation; basal cells; involucrin;
D O I
10.1002/pros.10244
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2003 Wiley-Liss, Inc.
引用
收藏
页码:206 / 218
页数:13
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