Enrichment and Interrogation of Cancer Stem Cells

Jarrar, Awad; Chumakova, Anastasia; Hitomi, Masahiro; Lathia, Justin D.

doi:10.1016/b978-0-12-803892-5.00003-6

Cited by 10 publications

(16 citation statements)

References 189 publications

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“…[17] Additionally, the expression of stem cell markers, including Oct3/4 and Sox2 are often used to examine stemness in potential CSCs. [31], [36], [37] To further demonstrate pluripotency, self-renewal capacity is measured by clonogenic assays and serial in vivo tumor initiation or limiting dilution experiments designed to examine whether a population could regenerate an entire tumor and thus be considered a CSC. [13], [14], [16], [38], [39] In order to differentiate tumor-initiating cells from CSCs, repeated tumor-initiating xenografts are required.…”

Section: Cd117+ Cells Are Cancer Stem-like Cellsmentioning

confidence: 99%

CD117/c-kit Defines a Prostate CSC-Like Subpopulation Driving Progression and TKI Resistance

Harris

Shi

Foster

et al. 2018

Preprint

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Cancer stem-like cells (CSCs) are associated with cancer progression, metastasis, and recurrence, and may also represent a subset of circulating tumor cells (CTCs). In our prior study, CTCs in advanced prostate cancer patients were found to express CD117/ckit in a liquid biopsy. Whether CD117 expression played an active or passive role in the aggressiveness and migration of these CTCs remained an open question. In this study, we show that CD117 expression in prostate cancer patients is associated with decreased overall and progression-free survival and that activation and phosphorylation of CD117 increases in prostate cancer patients with higher Gleason grades. To determine how CD117 expression and activation by its ligand stem cell factor (SCF, kit ligand, steel factor) alter prostate cancer aggressiveness, we used LNCaP-C4-2 and PC3-mm human prostate cancer cells, which contain a CD117+ subpopulation. We demonstrate that CD117+ cells display increased proliferation and migration. In prostaspheres, CD117 expression enhances sphere formation. In both 2D and 3D cultures, stemness marker gene expression is higher in CD117+ cells. Using xenograft limiting dilution assays and serial tumor initiation assays, we show that CD117+ cells represent a CSC population.Combined, these data indicate that CD117 expression potentially promotes tumor initiation and metastasis. Further, in cell lines, CD117 activation by SCF promotes faster proliferation and invasiveness, while blocking CD117 activation with tyrosine kinase inhibitors (TKIs) decreased progression in a context-dependent manner. We demonstrate that CD117 expression and activation drives prostate cancer aggressiveness through the CSC phenotype and TKI resistance.Harris 3

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Section: Cd117+ Cells Are Cancer Stem-like Cellsmentioning

confidence: 99%

CD117/c-kit Defines a Prostate CSC-Like Subpopulation Driving Progression and TKI Resistance

Harris

Shi

Foster

et al. 2018

Preprint

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“…Additional studies for self-renewal examine the formation of prostaspheres, which represent three-dimensional tumor progenitor structures [7]. In concert, expression of the stem cell markers Oct3/4 , Sox2 , Klf4 , Nanog , and c-Myc in CSCs are often used to examine stemness [20–22]. Several of these stem cell markers were upregulated in prostate cancer when compared to prostatitis or benign hyperplasia [23].…”

Section: What Is a Cancer Stem Cell?mentioning

confidence: 99%

Prostate Cancer Stem Cell Markers Drive Progression, Therapeutic Resistance, and Bone Metastasis

Harris

Kerr

2017

Stem Cells International

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Metastatic or recurrent tumors are the primary cause of cancer-related death. For prostate cancer, patients diagnosed with local disease have a 99% 5-year survival rate; however, this 5-year survival rate drops to 28% in patients with metastatic disease. This dramatic decline in survival has driven interest in discovering new markers able to identify tumors likely to recur and in developing new methods to prevent metastases from occurring. Biomarker discovery for aggressive tumor cells includes attempts to identify cancer stem cells (CSCs). CSCs are defined as tumor cells capable of self-renewal and regenerating the entire tumor heterogeneity. Thus, it is hypothesized that CSCs may drive primary tumor aggressiveness, metastatic colonization, and therapeutic relapse. The ability to identify these cells in the primary tumor or circulation would provide prognostic information capable of driving prostate cancer treatment decisions. Further, the ability to target these CSCs could prevent tumor metastasis and relapse after therapy allowing for prostate cancer to finally be cured. Here, we will review potential CSC markers and highlight evidence that describes how cells expressing each marker may drive prostate cancer progression, metastatic colonization and growth, tumor recurrence, and resistance to treatment.

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“…Such use of in vivo CSC functional assays has helped create the alternative interchangeably-used terms in the literature, such as “tumor-initiating cell” and “tumorigenic cell” to describe putative CSCs. In Box I, we list common methods to identify CSCs, including cell sorting-based transplantation [4, 21-29], lineage tracing [15, 30-34], barcode tracing [35], and other functional assays [36] for representative CSC markers in solid tumors, hematologic malignancies, and metastases. It is anticipated that pooled CRISPR/Cas-mediated gene editing and modulation would also be used in identifying tumorigenic drivers and regulator markers of CSCs in various cancers.…”

Section: Cscs Are Identified As Essential Therapeutic Targetsmentioning

confidence: 99%

“…Other complementary assays in vitro , such as spheres and reporter systems [36] which normally require validation analyses in vivo .…”

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confidence: 99%

New Opportunities and Challenges to Defeat Cancer Stem Cells

et al. 2017

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Cancer stem cells (CSCs) are a sub-population of cancer cells capable of self-renewal, proliferation, differentiation, plastic adaptation and immune regulation, thereby mediating tumorigenesis, metastasis and therapy resistance. CSCs are associated with cancer progression and clinical outcomes of cancer patients. Therefore successfully targeting CSCs is required to eradicate and cure cancer. Functional regulators of stem cell (stemness) signaling pathways in human cancers have brought new opportunities to target CSCs and reframe cancer-targeting strategies in clinical settings. However, challenges remain due to a lack of complete understanding of CSC plasticity/heterogeneity and limited efficacy of individual stemness inhibitors in cancer treatment. In this article, we review the CSC signaling pathways and the current state of CSC-targeting therapeutics in combinatory treatment in clinical trials.

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Enrichment and Interrogation of Cancer Stem Cells

Cited by 10 publications

References 189 publications

CD117/c-kit Defines a Prostate CSC-Like Subpopulation Driving Progression and TKI Resistance

CD117/c-kit Defines a Prostate CSC-Like Subpopulation Driving Progression and TKI Resistance

Prostate Cancer Stem Cell Markers Drive Progression, Therapeutic Resistance, and Bone Metastasis

New Opportunities and Challenges to Defeat Cancer Stem Cells

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