Primary Tumor Genotype Is an Important Determinant in Identification of Lung Cancer Propagating Cells

Curtis, Stephen J.; Sinkevicius, Kerstin W.; Li, Danan; Lau, Allison N.; Roach, Rebecca R.; Zamponi, Raffaella; Woolfenden, Amber; Kirsch, David G.; Wong, Kwok-Kin; Kim, Carla F.

doi:10.1016/j.stem.2010.05.021

Cited by 128 publications

(115 citation statements)

References 26 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: 69%

“…Similarly, CD133 + and CD133 -glioma cells may have different cells-of-origin [70]. There is evidence that the primary tumor genotypes dictate the overall phenotypes of tumor progenitors [44,66,110]. It is conceivable that more mature tumor-initiating cells derived from the primitive CSCs may sustain secondary genetic hits and in turn become new CSCs, and then develop independently of the original CSCs.…”

Section: Csc Heterogeneitymentioning

confidence: 99%

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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: 69%

Section: Csc Heterogeneitymentioning

confidence: 99%

Understanding cancer stem cell heterogeneity and plasticity

2012

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“…This is in contrast to recent claims that, in K-Ras and epidermal growth factor receptor (EGFR) models, 1 in 10,000 cells are tumor initiating (28). Although it is possible that Jenv tumors are fundamentally different than those driven by other oncogenes, it seems likely that tumor-initiating cell frequency is vastly underestimated in the aforementioned models.…”

Section: Discussionmentioning

confidence: 60%

“…However, although the previous study showed that 100% of lineage Recent reports suggest that one of the BASC markers, Sca-1, does enrich for tumor-propagating activity in mouse NSCLC, but this result is dependent on the nature of the primary oncogenic lesion (28). Interestingly, Sca-1 expression identified CSC in K-ras G12D /p53 À mice, but not in K-ras G12D alone or EGFR T790M-L858R -activated oncogene mouse models.…”

Section: Discussionmentioning

confidence: 89%

Lung Cancer in Mice Induced by the Jaagsiekte Sheep Retrovirus Envelope Protein Is Not Maintained by Rare Cancer Stem Cells, but Tumorigenicity Does Correlate with Wnt Pathway Activation

Vaughan

Halbert

Wootton

et al. 2012

Molecular Cancer Research

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JSRV, a simple beta-retrovirus, is the etiologic agent of ovine pulmonary adenocarcinoma, a form of non-small cell lung cancer in sheep and goats. It has been shown that the envelope protein alone is sufficient to induce tumorigenesis in the lungs of mice when delivered via an adeno-associated viral vector. Here, we tested the hypothesis that JSRV envelope-induced tumors are maintained by a small population of tumor-initiating cells, termed cancer stem cells. To test this hypothesis, dissociated cancer cells were sorted from envelope-induced tumors in mouse lung based on the putative stem cell markers Sca-1, CD34, and CD133, the pluripotency-associated transcription factor Oct4, and the level of Wnt signaling. No association with increased tumor-initiating capacity was found with any of the cell-surface markers. In addition, we were unable to detect any evidence of Oct4 expression in tumor-bearing mouse lung. However, tumor cells possessing an active Wnt signaling pathway did show a significant correlation with increased tumor formation upon transplantation. Limiting dilution transplant analysis suggests the existence of a large fraction of cells with the ability to propagate tumor growth, with increasing tumor initiation potential correlating with activated Wnt signaling. Mol Cancer Res; 10(1); 86-95. Ó2011 AACR.

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“…(59) Co-expression of CD133 and a6-integrin was observed in some but not all tumors. The genetic mutation profile may also influence the nature and phenotype of CSCs, as suggested by studies on different genetic mouse models of lung adenocarcinoma (60), whereas epigenetic changes in regulatory genes could impact marker expression itself. (64).…”

Section: Csc Conceptmentioning

confidence: 99%

Cancer Stem Cell Hypothesis: Implication for Cancer Prevention and Treatment

Meiliana

Dewi²,

Wijaya

2016

Indones Biomed J

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BACKGROUND: Cancer is a disease of genomic instability, evasion of immune cells, and adaptation of the tumor cells to the changing environment. Genetic heterogeneity caused by tumors and tumor microenvironmental factors forms the basis of aggressive behavior of some cancer cell populations.CONTENT: Cancers arise in self-renewing cell populations and that the resulting cancers, like their normal organ counterparts, are composed of hierarchically organized cell populations. Self – renewing “cancer stem cells” (CSC) maintain tumor growth and generate the diverse populations constituting the tumor bulk. CSCs in multiple tumor types have been demonstrated to be relatively resistant to radiation and chemotherapy. The clinical relevance of these studies has been supported by neoadjuvant breast cancer trials that demonstrated increases in the proportions of CSCs after therapy. The CSC hypothesis has tremendously important clinical implications.SUMMARY: In summary, a large and accumulating body of evidence supports the CSC hypothesis, which has important implications for cancer prevention and therapy. The ultimate test of this hypothesis will require clinical trials demonstrating that targeting of these pathways reduces cancer incidence and improves outcomes for patients with cancer.KEYWORDS: Somatic mutation, tumor heterogeneity, metastasis, epithelial-mesenchymal transition, CSC niche

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Primary Tumor Genotype Is an Important Determinant in Identification of Lung Cancer Propagating Cells

Cited by 128 publications

References 26 publications

Understanding cancer stem cell heterogeneity and plasticity

Understanding cancer stem cell heterogeneity and plasticity

Lung Cancer in Mice Induced by the Jaagsiekte Sheep Retrovirus Envelope Protein Is Not Maintained by Rare Cancer Stem Cells, but Tumorigenicity Does Correlate with Wnt Pathway Activation

Cancer Stem Cell Hypothesis: Implication for Cancer Prevention and Treatment

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