Characterization of benign and malignant prostate epithelial Hoechst 33342 side populations

Brown, Michael D.; Gilmore, Paul E; Hart, Claire A.; Samuel, J.; Ramani, Vijay; George, N. J. R.; Clarke, Noel W.

doi:10.1002/pros.20620

Cited by 94 publications

(71 citation statements)

References 67 publications

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“…The SP fraction has been identified in numerous cancers, including neuroblastoma, breast cancer, prostate cancer and gastrointestinal carcinoma, and their chemoresistance is due to the ability of multidrug-resistant stem/progenitor cells to efflux anticancer drugs such as mitoxanthrone, gemcitabine, doxorubicin or 5-fluorouracil [44, [101][102][103]. Moreover, in the presence of mitoxanthrone, the SP cell frequency in neuroblastoma was increased [102].…”

Section: Reviewmentioning

confidence: 99%

Cancer stem cell markers in common cancers – therapeutic implications

Klonisch

Wiecheć

Hombach‐Klonisch

et al. 2008

Trends in Molecular Medicine

358

286

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Section: Reviewmentioning

confidence: 99%

Cancer stem cell markers in common cancers – therapeutic implications

Klonisch

Wiecheć

Hombach‐Klonisch

et al. 2008

Trends in Molecular Medicine

358

286

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“…ABCG2 was shown to be efficient at Hoechst dye efflux, creating a side population (SP) phenotype that has been used as an alternate approach to identify multipotent stem cells in bone marrow, skeletal muscle, and neural tissue (Bunting 2002) and more recently in the prostate (Bhatt et al 2003). The SP cells of the prostate have slightly higher sphere-forming activity in vitro than the non-SP cells, although only by fourfold (Brown et al 2007). Further characterization showed that only 1% of the basal cells were included in the SP fraction, and they expressed known stem cell genes such as nestin, Bmi-1, hTeRT, and CD133 (Pascal et al 2007).…”

Section: Human Prostate Stem Cellsmentioning

confidence: 99%

Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression

Lukacs¹,

Lawson²,

Long-zuo³

et al. 2008

Cold Spring Harbor Symposia on Quantitative Biology

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Prostate cancer is a leading cause of cancer-related death in adult men. It can regress dramatically upon antihormonal therapy, but it often recurs in a more aggressive, androgen-independent form. Defining the prostate tissue stem cells (PrSCs) and their involvement in cancer initiation and maintenance may lead to better therapeutics. Using a tissue-regeneration model in which dissociated prostate epithelial cells mixed with inductive mesenchyme give rise to prostatic tubules, we have identified a small population of prostate cells that contains multiple stem cell characteristics. In this system, prostate cancer can be initiated by autocrine or paracrine growth factor signaling and intracellular overexpression of genes often found mutated in human prostate cancer. Using an in vitro prostate sphere assay, we further defined the PrSC population and demonstrated their selfrenewal and multilineage differentiation capabilities. Microarray analyses of the stem-and non-stem-cell populations have assisted us in finding and evaluating additional markers that can better define the PrSC population and further delineate the different cell types of the prostate, including those that serve as the target cell for tumor initiation.

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“…These include the cells that preferentially express CD44 (13), ␣2␤1 (i.e. ␣2␤1 hi ) (14), or CD133 (15,16) and the side population (17), whose phenotype is mediated by multidrug resistance family proteins, such as MDR-1 and ABCG2 (18). Interestingly, the ABCG2 ϩ cells in the benign prostate constitute Ͻ1% of total basal cell population and share essentially the same transcriptome as the side population cells (19).…”

mentioning

confidence: 99%

Critical and Distinct Roles of p16 and Telomerase in Regulating the Proliferative Life Span of Normal Human Prostate Epithelial Progenitor Cells

Bhatia

Jiang

Suraneni

et al. 2008

Journal of Biological Chemistry

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Normal human prostate (NHP) epithelial cells undergo senescence in vitro and in vivo, but the underlying molecular mechanisms remain obscure. Here we show that the senescence of primary NHP cells, which are immunophenotyped as intermediate basal-like cells expressing progenitor cell markers CD44, ␣2␤1, p63, hTERT, and CK5/CK18, involves loss of telomerase expression, up-regulation of p16, and activation of p53. Using genetically defined manipulations of these three signaling pathways, we show that p16 is the primary determinant of the NHP cell proliferative capacity and that hTERT is required for unlimited proliferative life span. Hence, suppression of p16 significantly extends NHP cell life span, but both p16 inhibition and hTERT are required to immortalize NHP cells. Importantly, immortalized NHP cells retain expression of most progenitor markers, demonstrate gene expression profiles characteristic of proliferating progenitor cells, and possess multilineage differentiation potential generating functional prostatic glands. Our studies shed important light on the molecular mechanisms regulating the proliferative life span of NHP progenitor cells.The prostatic glands contain neuroendocrine (NE) 7 cells and two epithelial cells: 1) luminal cells expressing cytokeratin 8 (CK8) and CK18, androgen receptor (AR), prostate-specific antigen (PSA), prostatic acid phosphatase, CD26, CD57, and 15-lipoxygenase 2 (15-LOX2) and 2) basal cells expressing CK5/CK14, CD44, CD104 (integrin ␤4), Bcl-2, p63, telomerase, and glutathione S-transferase-(1-3). It has been proposed that a common stem/progenitor cell may generate both basal and luminal cells (4). Alternatively, basal cells may function as progenitors to luminal cells (5, 6).The adult rodent prostate possesses regenerative stem cells (SCs) (6 -8). Whether adult human prostate contains definitive SCs is less certain, although there exists strong evidence that the basal cell layer harbors regenerative cells (1, 6, 9 -12), and several candidate populations of human prostate stem/progenitor cells, preferentially localized in the basal layer, have been reported. These include the cells that preferentially express CD44 (13), ␣2␤1 (i.e. ␣2␤1 hi ) (14), or CD133 (15, 16) and the side population (17), whose phenotype is mediated by multidrug resistance family proteins, such as MDR-1 and ABCG2 (18). Interestingly, the ABCG2 ϩ cells in the benign prostate constitute Ͻ1% of total basal cell population and share essentially the same transcriptome as the side population cells (19 * This work was supported, in whole or in part, by National Institutes of Health Grants R01-AG023374, R01-ES015888, and R21-ES015893-01A1. This work was also supported by American Cancer Society Grant RSG MGO-105961, Department of Defense Grants W81XWH-07-1-0616 and PC073751, the Prostate Cancer Foundation, the Elsa Pardee Foundation (to D. G. T.), and two Center Grants, CCSG-5 P30 CA166672 and ES07784. The costs of publication of this article were defrayed in part by the payment of page charges. This article m...

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Characterization of benign and malignant prostate epithelial Hoechst 33342 side populations

Cited by 94 publications

References 67 publications

Cancer stem cell markers in common cancers – therapeutic implications

Cancer stem cell markers in common cancers – therapeutic implications

Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression

Critical and Distinct Roles of p16 and Telomerase in Regulating the Proliferative Life Span of Normal Human Prostate Epithelial Progenitor Cells

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