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: J Bensimon, S Altmeyer-Morel, H Benjelloun, S Chevillard, J Lebeau
• Journal: Oncogene (Oncogene) Vol. 32 Issue 2 Pg. 251-8 (Jan 10 2013) ISSN: 1476-5594 [Electronic] England
• PMID: 22330142 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• CD24 Antigen
• Hyaluronan Receptors

Topics

• Biomarkers, Tumor (genetics, radiation effects)
• Breast Neoplasms (genetics, metabolism, radiotherapy)
• CD24 Antigen (analysis)
• Cell Line, Tumor
• Chromosome Breakage (radiation effects)
• Female
• Genomic Instability (radiation effects)
• Humans
• Hyaluronan Receptors (metabolism)
• Neoplastic Stem Cells (radiation effects)
• Polyploidy
• Radiation Tolerance (genetics)