Document Detail


Differentiation pathways and histogenetic aspects of normal and abnormal prostatic growth: a stem cell model.
MedLine Citation:
PMID:  8604398     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A stem cell model is presented for the organization of the prostatic epithelium that may explain normal and abnormal growth in the human prostate. This model is based on recent data indicating that: 1) The three basic cell types encountered in the prostatic epithelium--i.e., secretory luminal, basal, and endocrine paracrine (EP) cells--are linked in the precursor progeny relationship. 2) The proliferative compartment of the normal and hyperplastic epithelium is located in the basal cell layer. 3) The proliferative compartment of the prostatic epithelium is androgen-independent but contains andro-responsive target cells. 4) During the malignant transformation of the prostatic epithelium, the proliferative zone is inverted and shifts to luminal cell types. 5) Formation of neoplastic basement membrane (BM) material is crucial for the development of the invasive phenotype in prostate cancer. 6) The proliferative activities in prostate cancer are exclusively restricted to exocrine cell types, whereas endocrine differentiated tumor cells are postmitotic cells. 7) The majority of exocrine tumor cells are androgen-responsive in contrast to endocrine differentiated cell types that consistently lack the nuclear androgen receptor (AR). In this model, a small stem cell population located in the basal cell layer gives rise to all epithelial cell lineages encountered in the normal, hyperplastic, and neoplastic prostate. The differentiating process from basal cells to secretory luminal cells via intermediate phenotypes is induced by circulating androgens, and largely depends on the presence of androgen-responsive target cells in the basal cell layer. Accordingly, the abnormal growth of the secretory epithelium in benign prostate hyperplasia (BPH) may be related to an increase in the total number of androgen-responsive basal cells in the proliferative compartment. Prostate cancer derives from transformed stem cells located in the basal cell layer that acquire secretory luminal characteristics under androgenic stimulation. During tumor invasion, the malignant phenotypes adhere via specific receptors to newly formed BM-material, which, in turn, may facilitate their passage through the extracellular matrix. The occurrence of endocrine differentiation in prostate cancer reflects the pluripotency of its stem cells. The widespread absence of nuclear AR in endocrine differentiated tumor cells clearly indicates that this phenotype belongs to those cell clones in prostate cancer, that are initially androgen-independent and refractory to hormonal therapy. Accordingly, the progressive emergence of endocrine cell clones during tumor progression may represent one mechanism by which prostate cancer cells escape hormonal control.
Authors:
H Bonkhoff; K Remberger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  The Prostate     Volume:  28     ISSN:  0270-4137     ISO Abbreviation:  Prostate     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-05-14     Completed Date:  1996-05-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  98-106     Citation Subset:  IM    
Affiliation:
Institute of Pathology, University of the Saarland, Homburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / pathology*
Animals
Cell Differentiation
Cell Division
Cell Transformation, Neoplastic
Epithelial Cells
Epithelium / pathology
Humans
Male
Neoplasm Invasiveness
Phenotype
Prostate / cytology*,  pathology
Prostatic Hyperplasia / pathology*
Prostatic Neoplasms / pathology*
Receptors, Androgen / analysis
Stem Cells / cytology*,  pathology
Chemical
Reg. No./Substance:
0/Receptors, Androgen

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