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.

CD133-positive cancer stem cells from colo205 human colon adenocarcinoma cell line show resistance to chemotherapy and display a specific metabolomic profile

“…Tumor tissues have been shown to contain highly heterogeneous cell populations [2, 9, 17]. However, the role of each population and their interrelationships remain unclear and need to be determined to establish alternative effective diagnostic methods and therapeutics.…”

“…Previous studies have already described many markers to characterize CSCs [1, 9, 17]. Nevertheless, the presence of a universal marker for colon CSC characterization remains controversial.…”

“…Many studies have already reported the presence of CSCs in different solid tumors, such as breast, brain, prostate, lung, ovary, colon, pancreas, liver, melanoma, head and neck [4, 5, 6, 7]. The most common membrane markers used for the sorting or analysis of CSCs are CD133, CD44 and aldehyde dehydrogenase (ALDH1), while many other specific markers have also been described, such as CD24 and epithelial-specific antigen [3, 4, 8, 9, 10]. Nevertheless expression of these markers is highly heterogeneous, depending on cancer localization, cell type and the tumor microenvironment.…”

“…Another molecule, CD44, is expressed by a large number of mammalian cell types. This protein was first discovered on human hematopoietic stem cells and then identified in several cancers [4, 9]. Some studies also revealed that ALDH1, another common marker used for CSC identification, was also intimately correlated with tumorigenesis [1, 8, 15, 16].…”

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“…CSCs, as a unique population in tumor tissue, express stem cell markers and they also exhibit stem cell-like features such as self-renewing (13). It is known that breast cancer stem-like cells (BCSCs) are one of the causes of resistance against radio-and chemotherapy, leading to treatment failure (13)(14)(15). Although BCSCs are found in all subtypes of breast cancer, basal-type breast cancer tumors have higher population of BCSCs than luminal type breast cancer tumors (16,17).…”