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Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating–cancer stem cells: distinct, overlapping or same populations

Oncogene volume 30, pages 4609–4621 (2011)Cite this article

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Abstract

Cell populations of solid cancers and their distant models, the cancer cell lines, have been categorized in sub-populations: cancer stem–tumor-propagating cells (CSC–TPC) versus derived cells, epithelial- versus mesenchymal-type cells, dormant versus actively proliferating cells and so on. CSC–TPC are minimally defined by their operational properties: immortality and the ability to regenerate in vivo or in vitro the whole panel of cancer cells. The epithelial-to-mesenchymal transition (EMT), mostly observed in vitro, generates mesenchymal-type from epithelial-type cells. The converse transition is mesenchymal-to-epithelial transition. In vitro work suggests that CSC–TPC and EMT cell phenotypes overlap. An analysis of the properties of these sub-populations, as studied in vitro, shows that indeed these two phenotypes may be linked to some extent. However, the in vivo counterpart of this relation in human tumors has barely been investigated. A model in which among the EMT cells released from the tumor only the most competent CSC–TPC will succeed to metastasize is proposed. It is suggested that in the Darwinian evolution of cancer cells, many phenotypes reflecting the expression of various programs, reversible to irreversible, exclusive, overlapping or linked coexist and compete with each other.

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Author notes

  1. S Floor and W C G van Staveren: These authors contributed equally to this work.

Authors and Affiliations

  1. Faculty of Medicine, Institute of Interdisciplinary Research (IRIBHM), University of Brussels, Brussels, Belgium

    S Floor, W C G van Staveren, J E Dumont & C Maenhaut

  2. Faculty of Medicine, Institut Bordet, University of Brussels, Brussels, Belgium

    D Larsimont

  3. Faculty of Medicine, WELBIO, University of Brussels, Brussels, Belgium

    C Maenhaut

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  1. S Floor
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  2. W C G van Staveren
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  3. D Larsimont
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  4. J E Dumont
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Correspondence to J E Dumont.

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Appendix

Appendix

Pending questions

To understand the roles of EMT and of CSC–TPC in in vivo solid tumors, several points remain to be clarified, such as:

  1. 1

    Congruence of CSC–TPC markers in the purification by cell sorting of CSC–TPC from tumors.

  2. 2

    Congruence of immunohistochemical markers of CSC–TPC in tumors.

  3. 3

    Congruence of EMT immunohistochemical markers in tumors.

  4. 4

    Localization of embryonic SC–TPC in tumors.

  5. 5

    Localization of EMT cells in tumors and distinction between these and fibroblasts and inflammatory cells.

  6. 6

    Congruence of CSC–TPC and EMT markers in tumors.

  7. 7

    Congruence of CSC–TPC and EMT markers with markers of normal cell differentiation and proliferation.

  8. 8

    The relation of EMT cells and TPC with the metabolic geography of the tumor (for example, O2 availability).

  9. 9

    Definition of biomarkers of drug-persistent cells (drug-tolerant persisters) and slowly dividing cells (PKH), and eventual characterization of such cells in in vivo cancers.

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Floor, S., van Staveren, W., Larsimont, D. et al. Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating–cancer stem cells: distinct, overlapping or same populations. Oncogene 30, 4609–4621 (2011). https://doi.org/10.1038/onc.2011.184

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  • DOI: https://doi.org/10.1038/onc.2011.184

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