Association of reactive oxygen species levels and radioresistance in cancer stem cells

Abstract

Michael Clarke and colleagues find that cancer stem cell in breast tumours have lower levels of reactive oxygen species (ROS) than the rest of the tumour cells. This property renders cancer stem cells less sensitive to radiation therapy, which may cause radio resistance in breast cancer. This study shows that cancer stem cell in breast tumours have lower levels of reactive oxygen species (ROS) than the rest of the tumour cells. This property renders cancer stem cells less sensitive to radiation therapy, which may cause radioresistance in breast cancer. The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells1,2 and haematopoietic stem cells and early progenitors3,4,5,6 contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing7,8, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.