Stem Cell Characteristics in Prostate Cancer Cell Lines

Pfeiffer, Minja J.; Schalken, Jack A.

doi:10.1016/j.eururo.2009.01.015

Cited by 103 publications

(87 citation statements)

References 31 publications

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“…Much recent evidence indicates that PCa contains stem/progenitor cells that might play essential roles in prostate tumorigenicity and metastasis; therefore, the therapeutic strategies targeting these cells are emerging (Maitland & Collins 2008, Klarmann et al 2009, Pfeiffer & Schalken 2009, Li & Tang 2011. We speculate that the suppressor role of AR can be applied to the development of new therapies to target self-renewal/ proliferation of stem/progenitor cells and the basal cells as we observed in this study that introducing AR could block selfrenewal/proliferation of these cells.…”

Section: Using Orthotopic Injection Of Ck5supporting

confidence: 60%

Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells

Lee¹,

Tian²,

Huang³

et al. 2012

Journal of Endocrinology

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Early studies have reported the differential roles of androgen receptor (AR) in different types (luminal, basal intermediate, and stromal) of prostate cancer cells. In vivo mouse model tumor studies using the total prostate epithelial knockout mice (pes-ARKO) also revealed that AR played a suppressive role in proliferation of the CK5C luminal epithelial cells. Using three different resources (one human basal epithelial cell line, one mouse basal epithelial originated progenitor cell line, and a basal epithelium-specific ARKO mouse model), we here demonstrated that the AR in basal epithelial cells of normal prostate plays a suppressive role in their proliferation but a positive role in differentiation into luminal epithelial cells. These results led us to conclude that ARs may play a negative role to suppress CK5 C basal epithelial and progenitor cell proliferation, yet play an essential role to drive basal epithelial cells into more differentiated states. These results may explain why differential AR expression in different cell types within normal prostate is needed and suggest that ARs in prostate basal epithelial cells, although expressed at a very low level, are necessary to maintain the balance between progenitor cells and differentiated luminal epithelial cells.

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Section: Using Orthotopic Injection Of Ck5supporting

confidence: 60%

Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells

Lee¹,

Tian²,

Huang³

et al. 2012

Journal of Endocrinology

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“…Supporting this observation, enzymes in the cholesterol biosynthesis pathway have shown to be upregulated in CRPC (15). Additionally, a number of studies provide evidence for stemlike cells that may be the initiating population for a recurrent tumor in PCa (16)(17)(18)(19)(20). Whether adaptation to low androgen levels is initiated by PCa stem cells or by altering intracellular steroid metabolism is not yet known.…”

Section: Introductionmentioning

confidence: 99%

Steroidogenic Enzymes and Stem Cell Markers Are Upregulated during Androgen Deprivation in Prostate Cancer

Pfeiffer

Smit²,

Sedelaar

et al. 2011

Mol Med

100

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Considerable levels of testosterone and dihydrotestosterone (DHT) are found in prostate cancer (PCa) tissue after androgen deprivation therapy. Treatment of surviving cancer-initiating cells and the ability to metabolize steroids from precursors may be the keystones for the appearance of recurrent tumors. To study this hypothesis, we assessed the expression of several steroidogenic enzymes and stem cell markers in clinical PCa samples and cell cultures during androgen depletion. Gene expression profiles were determined by microarray or qRT-PCR. In addition, we measured cell viability and analyzed stem cell marker expression in DuCaP cells by immunocytochemistry. Seventy patient samples from different stages of PCa, and the PCa cell line DuCaP were included in this study. The androgen receptor (AR) and enzymes (AKR1C3, HSD17B2, HSD17B3, UGT2B15 and UGT2B17 ) that are involved in the metabolism of adrenal steroids were upregulated in castration resistant prostate cancer (CRPC). In vitro, some DuCaP cells survived androgen depletion, and eventually gave rise to a culture adapted to these conditions. During and after this transition, most of the steroidogenic enzymes were upregulated. These cells also are enriched with stem/progenitor cell markers cytokeratin 5 (CK5) and ATP-binding cassette sub-family G member 2 (ABCG2). Similarly, putative stem/progenitor cell markers CK5, c-Kit, nestin, CD44, c-met, ALDH1A1, α2-integrin, CD133, ABCG2, CXCR4 and POU5F1 were upregulated in clinical CRPC. The upregulation of steroidogenic enzymes and stem cell markers in recurrent tumors suggests that cancer initiating cells can expand by adaptation to their T/DHT deprived environment. Therapies targeting the metabolism of adrenal steroids by the tumor may prove effective in preventing tumor regrowth.

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“…4,5,7,9,11,12,35 Real-time qPCR analysis showed decreased expression levels of integrin ␣2 and CD44 in the ␣v-kd-Pro4luc cells ( Figure 3A). In line with these observations, flow cytometric analysis showed decreased protein levels of ␣2 integrin and CD44v6 in the ␣v-kd-Pro4luc cells.…”

Section: Differential Expression Of Stem/progenitor Markers and Invasmentioning

confidence: 99%

“…4 -6 CSCs have properties that resemble those of normal tissue stem cells, including the ability to self-renew, to reproducibly form tumors with the original cellular heterogeneity, and to undergo differentiation into more differentiated, nontumorigenic cells. 7 Increasing evidence suggests that normal stem cells and their immediate progenitors are prime targets for oncologic transformation. Collins and co-workers 4,8,9 have found that ␣2␤1-high/ CD44 ϩ /CD133 ϩ prostate cancer cells displayed enhanced clonogenic ability in vitro and form prostate-like glands in vivo.…”

mentioning

confidence: 99%

Integrin αv Expression Is Required for the Acquisition of a Metastatic Stem/Progenitor Cell Phenotype in Human Prostate Cancer

Hoogen

Horst

Cheung

et al. 2011

The American Journal of Pathology

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Integrins participate in multiple cellular processes, including cell adhesion, migration, proliferation, survival, and the activation of growth factor receptors. Recent studies have shown that expression of ␣v integrins is elevated in the prostate cancer stem/progenitor cell subpopulation compared with more differentiated, committed precursors. Here, we examine the functional role of ␣v integrin receptor expression in the acquisition of a metastatic stem/progenitor phenotype in human prostate cancer. Stable knockdown of ␣v integrins expression in PC-3M-Pro4 prostate cancer cells coincided with a significant decrease of prostate cancer stem/progenitor cell characteristics (␣2 integrin, CD44, and ALDH hi ) and decreased expression of invasion-associated genes Snail, Snail2, and Twist. Consistent with these observations, ␣v-knockdown strongly inhibited the clonogenic and migratory potentials of human prostate cancer cells in vitro and significantly decreased tumorigenicity and metastatic ability in preclinical models of orthotopic growth and bone metastasis. Our data indicate that integrin ␣v expression is functionally involved in the maintenance of a highly migratory, mesenchymal cellular phenotype as well as the acquisition of a stem/ progenitor phenotype in human prostate cancer cells with metastasis-initiating capacity. Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of death. The 5-year survival rate for men with organ-confined disease is almost 100% because of the current treatment options.

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Stem Cell Characteristics in Prostate Cancer Cell Lines

Cited by 103 publications

References 31 publications

Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells

Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells

Steroidogenic Enzymes and Stem Cell Markers Are Upregulated during Androgen Deprivation in Prostate Cancer

Integrin αv Expression Is Required for the Acquisition of a Metastatic Stem/Progenitor Cell Phenotype in Human Prostate Cancer

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