Cancer Stem Cells – Basic Biological Properties and Experimental Approaches

Abstract

Cancer stem cells (CSCs) are defined as a self‐renewing and self‐protecting subpopulation of tumour cells that can differentiate into all other tumour cell types found within a tumour. They can be prospectively identified and purified, either on the basis of specific cell surface marker expression, or by virtue of their biological properties; their self‐protection has been harnessed to develop several purification strategies, for example, side population or Aldefluor assays. Other prominent biological properties of CSCs include their exclusive clonogenicity and tumourigenicity. Many of these basic biological characteristics are shared between normal and CSCs, as are multiple signalling pathways regulating self‐renewal and differentiation. Unlike normal stem cells, CSCs often seem to be distinctly less stable, dynamically modulating their stemness and differentiation according to various environmental signals and/or genetic and epigenetic changes accumulated during the carcinogenic process. This plasticity of CSCs might underlie the prominent biological characteristics of malignant tumours, especially their propensity to metastasise.

Key Concepts:

  • Stem cells are long‐lived and protect their genome.

  • Existence of long‐lived, undifferentiated and self‐protecting cells could be indirectly inferred in tumours.

  • Cancer stem cells express specific cell surface markers and are amenable to differential staining procedures.

  • Cancer stem cells frequently exploit similar signalling pathways as embryonic stem cells and normal adult stem cells.

  • Hypoxia activates a multifaceted stem cell programme in tumours.

  • Cancer stem cell phenotype can be unstable, with repeated or even ongoing differentiation and dedifferentiation.

Keywords: cancer stem cells; cancer stem cell markers; stem cell self‐renewal and differentiation; cancer stem cell plasticity

Figure 1.

Two text‐book models of cancer cell growth and heterogeneity. The stochastic model (a) assumes that different subpopulations of tumour cells continuously arise and disappear by evolutionary processes like clonal selection. It is unable to prospectively isolate any subpopulation of tumour cells uniquely responsible for both perpetuating tumour growth and its spread to a secondary site, whereas in the hierarchical tumour model (b) only the CSCs are able to both perpetuate and transfer the tumour, by virtue of their exclusive self‐renewing ability.

Figure 2.

Hypoxia can impact on stem cell biology at multiple different levels, both by participating in the induction of Notch‐regulated genes (the leftmost pathway) and by directly inducing multiple genes involved in various aspects of stemness. Note that the individual effects can be partly contradictory – hypoxia can thus both induce the epithelial‐mesenchymal transition (EMT) and strenghten the epithelial character of cells.

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Hatina, Jiří, Fernandes, Maria Inès, Hoffmann, Michèle J, and Zeimet, Alain G(Sep 2013) Cancer Stem Cells – Basic Biological Properties and Experimental Approaches. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021164.pub2]