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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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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DOI: https://doi.org/10.1038/onc.2012.31
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