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: 22.15). 04/2009; 4(3):203-5. DOI: 10.1016/j.stem.2009.02.003
Source: PubMed

ABSTRACT 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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    • "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.
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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.
    Cellular and Molecular Neurobiology 06/2013; 33(6). DOI:10.1007/s10571-013-9951-6 · 2.20 Impact Factor
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    • "Finally, CSC nomenclature was adopted from normal tissue stem cells to describe the abilities required for maintaining tumor growth: self-renewal and giving rise to other tumor cells. The CSC concept and properties are frequently confused with the concept and properties of normal tissue stem cells (Jordan, 2009). The hierarchy of normal tissue stem cells is well defined and conserved. "
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    ABSTRACT: Eighty percent of malignant tumors that develop in the central nervous system are malignant gliomas, which are essentially incurable. Here, we discuss how recent sequencing studies are identifying unexpected drivers of gliomagenesis, including mutations in isocitrate dehydrogenase 1 and the NF-κB pathway, and how genome-wide analyses are reshaping the classification schemes for tumors and enhancing prognostic value of molecular markers. We discuss the controversies surrounding glioma stem cells and explore how the integration of new molecular data allows for the generation of more informative animal models to advance our knowledge of glioma's origin, progression, and treatment.
    Cell 03/2012; 149(1):36-47. DOI:10.1016/j.cell.2012.03.009 · 33.12 Impact Factor
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