Prostate Cancer Cells with Stem Cell Characteristics Reconstitute the Original Human Tumor <i>In vivo</i>

Gu, Guangyu; Yuan, Jianyong; Wills, Marcia L.; Kasper, Susan

doi:10.1158/0008-5472.can-06-4608

Cited by 317 publications

(266 citation statements)

References 48 publications

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“…Similarly, stem-like cancer cells have been reported in human cancers of the prostate [87][88][89][90][91][92][93][94][95][96][97][98][99][100], lung [101][102][103][104][105][106][107][108][109][110][111], and many other organs (liver, pancreas, kidney, bladder, ovary, etc). In prostate cancer, tumor-initiating cells have been identified in xenografts in CD44 + [90,96], CD44 + α2β1 + [91], TRA-1-60 + CD151 + CD166 + [99], and ALDH + [97,98] populations as well as in SP [87] and holoclones [94].…”

Section: Csc Heterogeneitymentioning

confidence: 70%

Understanding cancer stem cell heterogeneity and plasticity

2012

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Heterogeneity is an omnipresent feature of mammalian cells in vitro and in vivo. It has been recently realized that even mouse and human embryonic stem cells under the best culture conditions are heterogeneous containing pluripotent as well as partially committed cells. Somatic stem cells in adult organs are also heterogeneous, containing many subpopulations of self-renewing cells with distinct regenerative capacity. The differentiated progeny of adult stem cells also retain significant developmental plasticity that can be induced by a wide variety of experimental approaches. Like normal stem cells, recent data suggest that cancer stem cells (CSCs) similarly display significant phenotypic and functional heterogeneity, and that the CSC progeny can manifest diverse plasticity. Here, I discuss CSC heterogeneity and plasticity in the context of tumor development and progression, and by comparing with normal stem cell development. Appreciation of cancer cell plasticity entails a revision to the earlier concept that only the tumorigenic subset in the tumor needs to be targeted. By understanding the interrelationship between CSCs and their differentiated progeny, we can hope to develop better therapeutic regimens that can prevent the emergence of tumor cell variants that are able to found a new tumor and distant metastases.

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Section: Csc Heterogeneitymentioning

confidence: 70%

Understanding cancer stem cell heterogeneity and plasticity

2012

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“…Treatment of LNCaP with a combination of IL6 and enzalutamide led to a significant increase in stemness/self-renewal genes. The importance of these genes in prostate cancer could be demonstrated by several groups (47,48). Overexpression of SOCS3 was able to completely block the IL6/enzalutamide-mediated induction of the stemness genes, most likely due to the inhibition of STAT3 activity.…”

Section: Discussionmentioning

confidence: 97%

SOCS3 Modulates the Response to Enzalutamide and Is Regulated by Androgen Receptor Signaling and CpG Methylation in Prostate Cancer Cells

Handle

Erb

Luef

et al. 2016

Molecular Cancer Research

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The proinflammatory cytokine IL6 is associated with bad prognosis in prostate cancer and implicated in progression to castration resistance. Suppressor of cytokine signaling 3 (SOCS3) is an IL6-induced negative feedback regulator of the IL6/Janus kinase (JAK)/STAT3 pathway. This study reveals that the SOCS3 promoter is hypermethylated in cancerous regions compared with adjacent benign tissue in prostate cancer using methylation-specific qPCR. A series of in vitro experiments was performed to assess the functional impact of low SOCS3 expression during anti-androgen treatment. Using lentivirus-mediated knockdown, it was demonstrated for the first time that SOCS3 regulates IL6/JAK/STAT3 signaling in androgen receptor-positive LNCaP cells. In addition, SOCS3 mRNA is upregulated by the anti-androgens bicalutamide and enzalutamide. This effect is caused by androgen receptor-mediated suppression of IL6ST and JAK1 expression, which leads to altered STAT3 signaling. Functionally, knockdown of SOCS3 led to enhanced androgen receptor activity after 3 weeks of enzalutamide treatment in an inflammatory setting. Furthermore, the stemness/self-renewal associated genes SOX2 and NANOG were strongly upregulated by the long-term treatment, and modulation of SOCS3 expression was sufficient to counteract this effect. These findings prove that SOCS3 plays an important role during anti-androgen treatment in an inflammatory environment.Implications: SOCS3 is frequently inactivated by promoter hypermethylation in prostate cancer, which disrupts the feedback regulation of IL6 signaling and leads to reduced efficacy of enzalutamide in the presence of inflammatory cytokines.

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“…Although xenograft studies can be helpful, cell-line-based studies can be misleading due to cellular changes and selective pressures that can alter cancer cells in culture. Cells expressing embryonic stem cell (Oct4, Nanog, and Sox2) and early progenitor (CD44 and nestin) markers were found among immortalized primary human prostate cancer cells (Gu et al 2007). These cells could clonally reconstitute the original tumor in mice to contain all three prostate cell lineages, demonstrating some CSC properties.…”

Section: Cancer Stem Cells In Prostate Cancermentioning

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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Prostate Cancer Cells with Stem Cell Characteristics Reconstitute the Original Human Tumor In vivo

Cited by 317 publications

References 48 publications

Understanding cancer stem cell heterogeneity and plasticity

Understanding cancer stem cell heterogeneity and plasticity

SOCS3 Modulates the Response to Enzalutamide and Is Regulated by Androgen Receptor Signaling and CpG Methylation in Prostate Cancer Cells

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

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