Cancer Stem Cells: Controversial or Just Misunderstood?

James P. Wilmot Cancer Center, University of Rochester, 601 Elmwood Avenue, Box 704, Rochester, NY 14642, USA.
Cell stem cell (Impact Factor: 22.27). 04/2009; 4(3):203-5. DOI: 10.1016/j.stem.2009.02.003
Source: PubMed


While a broad range of expertise has recently come to bear on the intriguing topic of "cancer stem cells," the overall relevance of stem cells as they relate to cancer remains in dispute. In this commentary, underlying points of contention are described with the aim of defining focal points for discussion and future consideration.

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    • "Furthermore, CD44+/CD24low/- cells are more frequent in basal breast tumors (and particularly high in BRCA1 mutated tumors) suggesting that the cancer stem cells are not restricted to those markers [5]. Although there is no definitive consensus on the phenotype and frequency of CSCs in the majority of human solid tumor types, enough experimental evidence supports that many tumors of both epithelial and non-epithelial origin have functionally defined CSCs and that it affects tumor biology [6] [2]. "
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    ABSTRACT: Tumors are heterogeneous at the cellular level where the ability to maintain tumor growth resides in discrete cell populations. Floating sphere-forming assays are broadly used to test stem cell activity in tissues, tumors and cell lines. Spheroids are originated from a small population of cells with stem cell features able to grow in suspension culture and behaving as tumorigenic in mice. We tested the ability of eleven common breast cancer cell lines representing the major breast cancer subtypes to grow as mammospheres, measuring the ability to maintain cell viability upon serial non-adherent passage. Only MCF7, T47D, BT474, MDA-MB-436 and JIMT1 were successfully propagated as long-term mammosphere cultures, measured as the increase in the number of viable cells upon serial non-adherent passages. Other cell lines tested (SKBR3, MDA-MB-231, MDA-MB-468 and MDA-MB-435) formed cell clumps that can be disaggregated mechanically, but cell viability drops dramatically on their second passage. HCC1937 and HCC1569 cells formed typical mammospheres, although they could not be propagated as long-term mammosphere cultures. All the sphere forming lines but MDA-MB-436 express E-cadherin on their surface. Knock down of E-cadherin expression in MCF-7 cells abrogated its ability to grow as mammospheres, while re-expression of E-cadherin in SKBR3 cells allow them to form mammospheres. Therefore, the mammosphere assay is suitable to reveal stem like features in breast cancer cell lines that express E-cadherin.
    Full-text · Article · Oct 2013 · PLoS ONE
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    • "The original cancer stem cell model suggested that CSC represent a subset of cancer cells population which is well distinguishable by a limited number of cell-surface markers. During the time, many controversial issues regarding their origin , proportions in cancer cells population, heterogeneity , flexibility of their state, etc. have emerged [35] [36] [37] [38] [39] and the existence and role of CSC in cancer initiation and progression remain a topic of intense debate [40] [41] [42] [43] [44] [45]. Accordingly to Badve and Nakshatri [46], CSC should be viewed as representing an aggressive clone that has evolved during tumor progression , concluding that referring to these cells as CSC is, actually, a matter of semantics. "
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    ABSTRACT: Development of resistance limits transferability of most anticancer therapies into curative treatment and understanding mechanisms beyond it remains a big challenge. Many high resolution experimental observations show enormous intratumor heterogeneity at molecular, genetic and cellular levels which is made responsible for emerging resistance to therapy. Therefore, researchers search techniques to influence development of intratumor heterogeneity, which requires understanding its role within the context of integrative, logically consistent, framework, such as evolutionary theory. Although it is agreed that intratumor heterogeneity increases probability of the emergence of therapy resistant clones, more instructive role of its structure in the process of cancer dynamics and metastasis is needed. In the paper, intratumor heterogeneity is viewed as a product of two, in general stochastic, processes, evolutionary optimization and changing environment, respectively. In evolutionary theory, common risk-diversifying strategy displayed by isogenic populations in unpredictably changing environments is bet-hedging. We suggest, that the structure of intratumor heterogeneity is evolutionary trait evolving to maximize the clonal fitness in changing (or uncertain) environment and that its structure corresponds to bet-hedging strategy. We advocate our view by reviewing and combining important cancer relevant concepts.
    Full-text · Article · Jul 2013
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    • "In recent years, the cancer stem cell (CSC) hypothesis suggested that GBMs are mainly fueled by identifiable subpopulation of glioma stemlike cell (GSCs) with unlimited capacity for self-renewal, and effective therapeutic targeting of these CSCs might eradicate the capacity for prolonged tumor growth (Mao et al. 2009b; Singh et al. 2004). At present, the identity of GSCs is still ambiguous, probably due to inconsistent definitions from different groups, and the fact that GBMs are markedly interand intratumoral heterogeneous (Jordan 2009). For example, stem cell markers CD133 and CD15 are commonly used to identify GSCs (Mao et al. 2009a; Singh et al. 2004; Son et al. 2009). "
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    ABSTRACT: The biological functional roles of LGR5 (leucine-rich repeat containing G protein-coupled receptor 5, also known as GPR49), a novel potential marker for stem-like cells in glioblastoma (GSCs), is poorly acknowledged. Here, we demonstrated that LGR5 was detected in glioblastoma tissues and GSCs. Bioinformatics analysis revealed that LGR5 is closely related to neurogenesis and neuronal functions, and preferentially expressed in Proneural subtype of GBMs. Furthermore, LGR5 is regulated by Proneural factor OLIG2, which is important for both neurogenesis and GSC maintenance. Biological experiments in GSC cells validated the bioinformatics analysis results and revealed that LGR5 regulated the tumor sphere formation capacity, an important stem cell property for GSCs. Therefore, LGR5 expression may be functionally correlated with the neurogenic competence, and be regulated by OLIG2 in GSCs.
    Full-text · Article · Jun 2013 · Cellular and Molecular Neurobiology
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