Association of Reactive Oxygen Species Levels and Radioresistance in Cancer Stem Cells

By M. Diehn, Robert W. Cho, N. Lobo, T. Kalisky, M. Dorie, A. Kulp, Dalong Qian, Jessica S. Lam, Laurie E. Ailles, Manzhi Wong and 13 more. Nature, 2009

2,481 citations recorded by the source corpus.

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 cells and haematopoietic stem cells and early progenitors 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 killing, 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.

Subfields: Molecular Biology, Oncology, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/8658ed1af891c01099ef289a19bcf058aa1b9c30

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. R. Weinberg
2. Rahul Satija
3. Nir Yosef
4. Guido Kroemer
5. L. Galluzzi
6. John C. Marioni
7. J. Dick
8. Eric S. Lander

In Oncology

1. R. Weinberg
2. J. Dick
3. Antonija Krešo
4. Guido Kroemer
5. S. Morrison
6. L. Galluzzi
7. J. Medema
8. C. Lord

In Radiology, Nuclear Medicine and Imaging

1. Marco Durante
2. Guido Kroemer
3. R. Weinberg
4. Jay S. Loeffler

Citations in the corpus

• Oxidative stress, inflammation, and cancer: how are they linked? (2010, neutral): “corresponding nontumorigenic cells [295].”
• Evolution of the cancer stem cell model. (2014, background): “…resistance in glioblastoma, colon cancer, breast cancer, and numerous other tumors, where studies show that T-IC fractions are more resistant to therapy compared to non-T-IC (Bao et al., 2006; Diehn et al., 2009; Ishikawa et al., 2007; Saito et al., 2010; Viale et al., 2009; Zhang et al., 2010).”
• Immunosenescence: molecular mechanisms and diseases (2023, background): “Low ROS levels in HSCs and early progenitor cells are essential to maintain their stemness potential compared with that of late differentiated progeny cells.(76) However, ROS gradually accumulate with the degradation of oxidized proteins by ATP-induced mitochondrial Lon proteases and an impaired mit”
• Chemotherapy Resistant Human Acute Myeloid Leukemia Cells are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism (2017, background): “In Vivo RLCs Have Elevated ROS Levels and Active Mitochondria after AraC Treatment On the basis of the literature (30, 31) and on our transcriptomic signature of RLCs enriched in inflammatory, stress, and ROS responses, we hypothesized that in vivo AraC chemotherapy could induce redox alteration and”
• Cancer stem cells: impact, heterogeneity, and uncertainty. (2012, background): “Evidence has also been presented for radiation resistance in brain tumor-initiating cells (Bao et al., 2006) and breast cancerinitiating cells (Diehn et al., 2009).”
• Metabolic regulation of hematopoietic stem cells in the hypoxic niche. (2011, background): “These activities may be relevant to cancer stem cells (CSCs), which show low levels of ROS (Diehn et al., 2009).”
• Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? (2009, background): “Recent studies showed that normal haemopoietic stem cells and normal mammary epithelial stem cells maintained ROS at lower levels than their mature progeny to prevent cellular differentiation and maintain long-term self-renewa”
• Identification of selective inhibitors of cancer stem cells by high-throughput screening (2009, background): “CSCs are resistant to many current cancer treatments, including chemo- and radiation therapy (Bao et al., 2006; Dean et al., 2005; Diehn et al., 2009; Diehn and Clarke, 2006; Eyler and Rich, 2008; Li et al., 2008; Woodward et al., 2007).”