期刊
EUROPEAN UROLOGY
卷 53, 期 3, 页码 524-532出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.eururo.2007.11.028
关键词
adult stem cells; cell differentiation; mesenchymal stem cells; prostate gland
Objectives: Questions regarding the cell source and mechanisms in the initiation and progression of prostate cancer are today still open for debate. Indeed, our knowledge regarding prostate cell regulation, self-renewal, and cytodifferentiation is presently rather limited. In this study, we investigated these processes in the normal adult human prostate. Methods: Dynamic expression patterns in prostate stem/progenitor cells, intermediate/transit-amplifying cells, and cell lineages were immunohistochemically identified in an in situ explant renewal model of the human normal/benign adult prostate (n = 6). Results: Cells with a basal phenotype proliferated significantly in explant cultures, whereas luminal cells went into apoptosis. Results further show down-regulation in tissue cultures of the basal and hypothetical stem cell marker Bcl-2 in the majority of cells, except in rare putative epithelial stem cells. Investigation of established (AC133) and novel candidate prostate stem/progenitor markers, including the cell surface receptor tyrosine kinase KIT and its ligand stem cell factor (SCF), showed that these rare epithelial cells are AC133(+)/CD133(low)/Bcl-2(high)/cytokeratin(+)/vimentin(-)/KIT(low)/SCF(low). In addition, we report on a stromal population that expresses the mesenchymal marker vimentin and that is AC133(-)/CD133(high)/Bcl-2(-)/cytokeratin(-)/KIT(high)/SCF(high). Conclusions: We provide evidence for epithelial renewal in response to tissue culture and for basal and epithelial stem/progenitor cell recruitment leading to an expansion of an intermediate luminal precursor phenotype. Data further suggest that SCF regulates prostate epithelial stem/progenitor cells in an autocrine manner and that all or a subset of the identified novel stromal phenotype represents prostate stromal progenitor cells or interstitial pacemaker cells or both. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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