Prostate Stem Cells in the Development of Benign Prostate Hyperplasia and Prostate Cancer: Emerging Role and Concepts

Prajapati, Akhilesh; Gupta, Sharad; Mistry, Bhavesh V.; Gupta, Sarita

doi:10.1155/2013/107954

Cited by 41 publications

(33 citation statements)

References 112 publications

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“…Understanding of the prostate stem cell biology is essential since there is a growing body of evidence suggesting that benign prostate hyperplasia and prostate cancer may arise from the stem or stem-like cell compartments [30]. In this study, we took advantage of the s-SHIP promoter-driven reporter to detect and isolate s-SHIP-expressing human prostate cells.…”

Section: Discussionmentioning

confidence: 99%

Enrichment of Human Stem-Like Prostate Cells with s-SHIP Promoter Activity Uncovers a Role in Stemness for the Long Noncoding RNA H19

Roy

Vennin

Brocqueville

et al. 2015

Stem Cells and Development

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Understanding normal and cancer stem cells should provide insights into the origin of prostate cancer and their mechanisms of resistance to current treatment strategies. In this study, we isolated and characterized stem-like cells present in the immortalized human prostate cell line, RWPE-1. We used a reporter system with green fluorescent protein (GFP) driven by the promoter of s-SHIP (for stem-SH2-domain-containing 5¢-inositol phosphatase) whose stem cell-specific expression has been previously shown. We observed that s-SHIP-GFPexpressing RWPE-1 cells showed stem cell characteristics such as increased expression of stem cell surface markers (CD44, CD166, TROP2) and pluripotency transcription factors (Oct4, Sox2), and enhanced sphereforming capacity and resistance to arsenite-induced cell death. Concomitant increased expression of the long noncoding RNA H19 was observed, which prompted us to investigate a putative role in stemness for this oncofetal gene. Targeted suppression of H19 with siRNA decreased Oct4 and Sox2 gene expression and colonyforming potential in RWPE-1 cells. Conversely, overexpression of H19 significantly increased gene expression of these two transcription factors and the sphere-forming capacity of RWPE-1 cells. Analysis of H19 expression in various prostate and mammary human cell lines revealed similarities with Sox2 expression, suggesting that a functional relationship may exist between H19 and Sox2. Collectively, we provide the first evidence that s-SHIP-GFP promoter reporter offers a unique marker for the enrichment of human stem-like cell populations and highlight a role in stemness for the long noncoding RNA H19.

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Section: Discussionmentioning

confidence: 99%

Enrichment of Human Stem-Like Prostate Cells with s-SHIP Promoter Activity Uncovers a Role in Stemness for the Long Noncoding RNA H19

Roy

Vennin

Brocqueville

et al. 2015

Stem Cells and Development

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“…The similarities between tissue development and adult tissue regeneration suggested a critical role of pluripotent cells in inflammation-induced tissue repair. Pluripotent prostate epithelial progenitor cells have been identified in normal prostate, BPH, and prostate cancer tissues (25,33). They were capable of regenerating other prostate cells, such as basal cell and luminal cells, in vitro or in vivo (19,21,24).…”

mentioning

confidence: 99%

Expansion of prostate epithelial progenitor cells after inflammation of the mouse prostate

Wang

Zoetemelk

Chitteti

et al. 2015

American Journal of Physiology-Renal Physiology

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Prostatic inflammation is a nearly ubiquitous pathological feature observed in specimens from benign prostate hyperplasia and prostate cancer patients. The microenvironment of the inflamed prostate is highly reactive, and epithelial hyperplasia is a hallmark feature of inflamed prostates. How inflammation orchestrates epithelial proliferation as part of its repair and recovery action is not well understood. Here, we report that a novel epithelial progenitor cell population is induced to expand during inflammation. We used sphere culture assays, immunofluorescence, and flow cytometry to show that this population is increased in bacterially induced inflamed mouse prostates relative to naïve control prostates. We confirmed from previous reports that this population exclusively possesses the ability to regrow entire prostatic structures from single cell culture using renal grafts. In addition, putative progenitor cells harvested from inflamed animals have greater aggregation capacity than those isolated from naïve control prostates. Expansion of this critical cell population requires IL-1 signaling, as IL-1 receptor 1-null mice exhibit inflammation similar to wild-type inflamed animals but exhibit significantly reduced progenitor cell proliferation and hyperplasia. These data demonstrate that inflammation promotes hyperplasia in the mouse prostatic epithelium by inducing the expansion of a selected epithelial progenitor cell population in an IL-1 receptor-dependent manner. These findings may have significant impact on our understanding of how inflammation promotes proliferative diseases such as benign prostatic hyperplasia and prostate cancer, both of which depend on expansion of cells that exhibit a progenitor-like nature.

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“…It is characterized by hyperplasia of epithelial and stromal cells in the transition zone of the prostate gland, which can be observed histopathologically [24]. Stem cells in the human prostate have been identified and isolated using the cell surface markers such as CD44 [25], integrin α2β1 [26], CD133 (Prominin-1) [27] which, are believed to be responsible for the development and progression of proliferative disorders of the prostate such as prostate cancer and benign prostate hyperplasia [9,[28][29][30]. Based on high expression of α2β1 integrin, Collins and colleagues identified PSCs in the basal layer and showed that the α2β1 high integrin cells represent ~1% of basal cell population in the human prostate [26].…”

Section: Discussionmentioning

confidence: 99%

Pluripotent Stem Cell within the Prostate could be Responsible for Benign Prostate Hyperplasia in Human

Prajapati¹

2014

J Stem Cell Res Ther

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Aim: Abnormal prostate growth is the most prevalent pathological sign in aged human males, reflected by high incidence of Benign Prostatic Hyperplasia (BPH) and Prostate Cancer (PCa). The successful isolation and cultivation of prostate cells, is a prerequisite need for establishing a model cell line for understanding the pathogenesis, unique biological properties and also various evidences suggest the role of stem cells in the pathogenesis of these conditions for a therapeutic point of view. Methods and results: Here we isolated a candidate pluripotent stem cell population from BPH patients underwent TURP which include the isolation of an enriched population of prostate stem cells through cell culture techniques and the cultivation of prostate stem cells in vitro and characterization of these cells and their stem potential, including in-vivo teratoma generation. Cytogenetic analysis by G-banding assay demonstrated an aneuploid karyotype with a model chromosome number of 60 and normal Y chromosome. Characterization of isolated cells showed the presence of ONS pluripotency stem cell markers. Beside this these cells were also found positive for stem cell surface markers such as CD49b, CD44, CD117, CD34 and prostatic tissue specific markers like p63 and Androgen Receptor. In-vitro differentiation of the cells demonstrated formation of a tri-germinal layer into ectodermal, endodermal and mesodermal cell lineages with defined medium conditions and In-vivo teratoma formation in excised tumor in Balb/c mouse. Conclusion: we report here isolation, establishment and characterization of human prostate-derived pluripotent stem cell line. The cell line eventually serves as a potential tool for studies in prostate adult stem cell research, understanding etiopathophysiology and the regulation of BPH and PCa.

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Prostate Stem Cells in the Development of Benign Prostate Hyperplasia and Prostate Cancer: Emerging Role and Concepts

Cited by 41 publications

References 112 publications

Enrichment of Human Stem-Like Prostate Cells with s-SHIP Promoter Activity Uncovers a Role in Stemness for the Long Noncoding RNA H19

Enrichment of Human Stem-Like Prostate Cells with s-SHIP Promoter Activity Uncovers a Role in Stemness for the Long Noncoding RNA H19

Expansion of prostate epithelial progenitor cells after inflammation of the mouse prostate

Pluripotent Stem Cell within the Prostate could be Responsible for Benign Prostate Hyperplasia in Human

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