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CD24−/low stem-like breast cancer marker defines the radiation-resistant cells involved in memorization and transmission of radiation-induced genomic instability

Oncogene volume 32, pages 251–258 (2013)Cite this article

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Abstract

A growing body of evidence attributes properties of chemo- and/or radiation-resistance to cancer stem cells (CSCs). Moreover, non-targeted delayed effects such as genomic instability, transmitted through many generations, can be observed in the progeny of surviving irradiated cells. As a consequence, we propose that radiation-resistance properties associated to CSCs could confer a key role to this subpopulation in the transmission of genomic instability. To test this hypothesis, we searched the CSC markers associated to radiation-resistance in breast cancer cell lines and studied the role of the resistant cells in the transmission of genomic instability. First, we show that irradiation induces a 2–4 weeks period of intense cell death leading to the emergence of chromosomal unstable cells during more than 35 population doublings. Then, among seven breast CSC markers, we identify CD24−/low labelling as a marker of radiation-resistance. We demonstrate that CD24+ progeny of irradiated cells exclusively descends from CD24−/low cells. Finally, we show that delayed chromosomal instability is only expressed by CD24+ cells, but is transmitted by stable surviving CD24−/low cells. So, for the first time a CSC marker, CD24, is associated with the transmission of genomic instability. This work may assign a new deleterious role to breast CSCs in aggressive recurrence after radiotherapy, as the transmitted genomic instability potentially leads tumour cells to acquire more aggressive characteristics.

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Acknowledgements

We thank Dr P-H. Romeo for constructive criticism on this manuscript. We also thank Drs J Baijer, D Lewandowski and P Fouchet for flow cytometry technical assistance and advices. This work was supported by grants from Electricité de France (EDF) and from MELODI and DoReMi Networks.

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Authors and Affiliations

  1. CEA, DSV, iRCM, SREIT, Laboratoire de Cancérologie Expérimentale (LCE), Fontenay-aux-Roses, France

    J Bensimon, S Altmeyer-Morel, S Chevillard & J Lebeau

  2. CEA, DSV, iRCM, SCSR, plateforme de tri cellulaire, Fontenay-aux-Roses, France

    H Benjelloun

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  1. J Bensimon
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  2. S Altmeyer-Morel
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  3. H Benjelloun
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Correspondence to J Lebeau.

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Bensimon, J., Altmeyer-Morel, S., Benjelloun, H. et al. CD24−/low stem-like breast cancer marker defines the radiation-resistant cells involved in memorization and transmission of radiation-induced genomic instability. Oncogene 32, 251–258 (2013). https://doi.org/10.1038/onc.2012.31

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