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

@article{citeulike:4012802, abstract = {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.}, author = {Diehn, Maximilian and Cho, Robert W. and Lobo, Neethan A. and Kalisky, Tomer and Dorie, Mary J. and Kulp, Angela N. and Qian, Dalong and Lam, Jessica S. and Ailles, Laurie E. and Wong, Manzhi and Joshua, Benzion and Kaplan, Michael J. and Wapnir, Irene and Dirbas, Frederick M. and Somlo, George and Garberoglio, Carlos and Paz, Benjamin and Shen, Jeannie and Lau, Sean K. and Quake, Stephen R. and Brown, J. Martin and Weissman, Irving L. and Clarke, Michael F.}, citeulike-article-id = {4012802}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature07733}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature07733}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19194462}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19194462}, day = {04}, doi = {10.1038/nature07733}, issn = {0028-0836}, journal = {Nature}, keywords = {csc}, month = {February}, number = {7239}, pages = {780--783}, posted-at = {2009-11-02 16:04:29}, priority = {2}, publisher = {Nature Publishing Group}, title = {Association of reactive oxygen species levels and radioresistance in cancer stem cells}, url = {http://dx.doi.org/10.1038/nature07733}, volume = {458}, year = {2009} }

TY - JOUR ID - citeulike:4012802 L3 - citeulike-article-id:4012802 N2 - 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. IS - 7239 JF - Nature SN - 0028-0836 EP - 783 TI - Association of reactive oxygen species levels and radioresistance in cancer stem cells PB - Nature Publishing Group VL - 458 SP - 780 KW - csc AU - Diehn, Maximilian AU - Cho, Robert AU - Lobo, Neethan AU - Kalisky, Tomer AU - Dorie, Mary AU - Kulp, Angela AU - Qian, Dalong AU - Lam, Jessica AU - Ailles, Laurie AU - Wong, Manzhi AU - Joshua, Benzion AU - Kaplan, Michael AU - Wapnir, Irene AU - Dirbas, Frederick AU - Somlo, George AU - Garberoglio, Carlos AU - Paz, Benjamin AU - Shen, Jeannie AU - Lau, Sean AU - Quake, Stephen AU - Brown, Martin AU - Weissman, Irving AU - Clarke, Michael PY - 2009/02/04/ UR - http://dx.doi.org/10.1038/nature07733 ER -