Radiation-Induced Reprogramming of Pre-Senescent Mammary Epithelial Cells Enriches Putative CD44+/CD24−/low Stem Cell Phenotype
Year: 2016
Type: article
Abstract: The enrichment of putative CD44(+)/CD24(-/low) breast stem cell populations following exposure to ionizing radiation (IR) has been ascribed to their inherent radioresistance and an elevated frequency of symmetric division during repopulation. However, recent studies demonstrating radiation-induced phenotypic reprogramming (the transition of non-CD44(+)/CD24(-/low) cells into the CD44(+)/CD24(-/low) phenotype) as a potential mechanism of CD44(+)/CD24(-/low) cell enrichment have raised the question of whether a higher survival and increased self-renewal of existing CD44(+)/CD24(-/low) cells or induced reprogramming is an additional mode of enrichment. To investigate this question, we combined a cellular automata model with in vitro experimental data using both MCF-10A non-tumorigenic human mammary epithelial cells and MCF-7 breast cancer cells, with the goal of identifying the mechanistic basis of CD44(+)/CD24(-/low) stem cell enrichment in the context of radiation-induced cellular senescence. Quantitative modeling revealed that incomplete phenotypic reprogramming of pre-senescent non-stem cells (reprogramming whereby the CD44(+)/CD24(-/low) phenotype is conveyed, along with the short-term proliferation capacity of the original cell) could be an additional mode of enriching the CD44(+)/CD24(-/low) subpopulation. Furthermore, stem cell enrichment in MCF-7 cells occurs both at lower doses and earlier time points, and has longer persistence, than that observed in MCF-10A cells, suggesting that phenotypic plasticity appears to be less regulated in breast cancer cells. Taken together, these results suggest that reprogramming of pre-senescent non-stem cells may play a significant role in both cancer and non-tumorigenic mammary epithelial populations following exposure to IR, a finding with important implications for both radiation therapy and radiation carcinogenesis.
Source: Frontiers in Oncology
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Awards: THE ENDS OF HUMAN CHROMOSOMES ARE CAPPED BY TELOMERES, TANDEM ARRAYS OF REPETITIVE DNA SEQUENCE AND ASSOCIATED PROTEINS, WHICH SERVE TO PROTECT CHROM, TELOMERIC PROTEINS IN THE RADIATION/DNA DAMAGE RESPONSE THIS RESEARCH ADDRESSES RADIATION HEALTH BIOASTRONAUTICS ROADMAP (BR) CARCINOGENESIS QUESTIO, G2018804017, THE GOAL OF OUR INVESTIGATION IS TO PROVIDE MULTI-SCALE DATA FOR AN IMPROVED MECHANISTIC UNDERSTANDING, AND AN AUGMENTED CONCEPTUAL FRAMEWORK FOR NAS, G6404814513
OpenAlex ID: W2410119082