title: CD24(-/low) stem-like breast cancer marker defines the radiation-resistant cells involved in memorization and transmission of radiation-induced genomic instability.
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.
authors.affiliation: CEA, DSV, iRCM, SREIT, Laboratoire de Cancérologie Expérimentale (LCE), Fontenay-aux-Roses, France.
authors.forename: J
authors.initials: J
authors.lastname: Bensimon
authors.forename: S
authors.initials: S
authors.lastname: Altmeyer-Morel
authors.forename: H
authors.initials: H
authors.lastname: Benjelloun
authors.forename: S
authors.initials: S
authors.lastname: Chevillard
authors.forename: J
authors.initials: J
authors.lastname: Lebeau
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000528:radiation effects; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D051927:CD24 Antigen / Q000032:analysis*; D045744:Cell Line, Tumor; D019457:Chromosome Breakage / Q000528:radiation effects; D005260:Female; D042822:Genomic Instability / Q000528:radiation effects*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000528:radiation effects; D011123:Polyploidy; D011836:Radiation Tolerance / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D018960:Hyaluronan Receptors