CD24(-/low) stem-like breast cancer marker defines the radiation-resistant cells involved in memorization and transmission of radiation-induced genomic instability.
Oncogene. 2012 Feb 13. Epub 2012 Feb 13. PMID: 22330142
CEA, DSV, iRCM, SREIT, Laboratoire de Cancérologie Expérimentale (LCE), Fontenay-aux-Roses, France.
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.Oncogene advance online publication, 13 February 2012; doi:10.1038/onc.2012.31.