Laboratory of Experimental Cancerology, Institute of Cellular and Molecular Radiobiology, Genetic Stability Stem Cells and Radiation, François Jacob Institute of Biology, French Alternative Energies and Atomic Energy Commission (CEA), Paris University and Paris‑Saclay University, F‑92265 Fontenay‑aux‑Roses, France.
Unit of Prion Disorders and Related Infectious Agents, François Jacob Institute of Biology, CEA, Paris‑Saclay University, F‑92265 Fontenay‑aux‑Roses, France.
Oncol Rep. 2023 Jan;49(1). doi: 10.3892/or.2022.8441. Epub 2022 Nov 11.
Cancer stem cells (CSCs) serve an essential role in failure of conventional antitumor therapy. In breast cancer, CD24/CD44 phenotype and high aldehyde dehydrogenase activity are associated with CSC subtypes. Furthermore, CD24/CD44 pattern is also characteristic of mesenchymal cells generated by epithelial‑mesenchymal transition (EMT). CD24 is a surface marker expressed in numerous types of tumor, however, its biological functions and role in cancer progression and treatment resistance remain poorly documented. Loss of CD24 expression in breast cancer cells is associated with radiation resistance and control of oxidative stress. Reactive oxygen species (ROS) mediate the effects of anticancer drugs as well as ionizing radiation; therefore, the present study investigated if CD24 mediates radiation‑ and chemo‑resistance of breast cancer cells. Using a HMLE breast cancer cell model, CD24 expression has been artificially modulated and it was observed that loss of CD24 expression induced stemness properties associated with acquisition of a hybrid E/M phenotype. CD24 cells were more radiation‑ and chemo‑resistant than CD24 cells. The resistance was associated with lower levels of ROS; CD24 controlled ROS levels via regulation of mitochondrial function independently of antioxidant activity. Together, these results suggested a key role of CD24 in de‑differentiation of breast cancer cells and promoting acquisition of therapeutic resistance properties.
癌症干细胞（CSCs）在常规抗肿瘤治疗失败中起着至关重要的作用。在乳腺癌中，CD24/CD44 表型和高醛脱氢酶活性与 CSC 亚型相关。此外，CD24/CD44 模式也是上皮-间充质转化（EMT）产生的间充质细胞的特征。CD24 是一种在多种类型的肿瘤中表达的表面标志物，然而，其生物学功能及其在癌症进展和治疗耐药性中的作用仍记录甚少。乳腺癌细胞中 CD24 表达的缺失与辐射抗性和氧化应激的控制有关。活性氧（ROS）介导抗癌药物以及电离辐射的作用；因此，本研究探讨了 CD24 是否介导乳腺癌细胞的辐射和化疗耐药性。使用 HMLE 乳腺癌细胞模型，人工调节 CD24 表达，观察到 CD24 表达缺失诱导与获得混合 E/M 表型相关的干细胞特性。与 CD24 细胞相比，CD24 细胞对辐射和化疗的耐药性更强。耐药性与较低的 ROS 水平有关；CD24 通过独立于抗氧化活性的调节线粒体功能来控制 ROS 水平。总之，这些结果表明 CD24 在乳腺癌细胞去分化和促进获得治疗耐药性特性方面发挥着关键作用。
