斯坦福大学干细胞生物学和再生医学研究所，放射肿瘤治疗研究中心，儿科干细胞移植分部，霍华休斯医学研究所生物工程系等处的研究人员找出了癌症干细胞中活性氧簇水平与抗辐射性的内在关联，相关成果公布在最新一期的Nature上。
氧是人类生存必不可少的物质，但是在氧气的代谢过程中可能产生一种名为“活性氧簇”的物质，这一类物质对人体丝毫没有好处，它常常与癌症、心血管疾病以及老化有着千丝万缕的关系。
近期的研究发现，中枢神经细胞干细胞，造血干细胞和早期的其他祖细胞成熟前所含的“活性氧簇”水平比成熟后要低，据说，这一差别对维持干细胞的功能具有关键的意义。研究者推测，上皮组织干细胞与上皮组织癌症干细胞可能也具有类似的特征。以乳房上皮细胞为例，研究者发现，乳房上皮细胞成熟前的活性氧簇的含量比成熟后低。值得关注的是，人类和鼠类的乳腺癌干细胞亚群细胞比正常细胞的活性氧簇的含量低。
研究小组发现，低水平的活性氧簇有助癌症干细胞表达自由基清除系统。从药理学意义上来说，缺失活性氧簇的清除系统癌症干细胞的集落生成能力降低，导致癌症干细胞对辐射敏感。这些研究结果表明，部分癌症干细胞的亚细胞群与正常的组织干细胞相似，含有低水平的活性氧簇，与非致瘤性的祖细胞相比，这些细胞清除自由基的能力更强，这也可能是肿瘤细胞对辐射产生耐受性的一个机制。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature advance online publication 4 February 2009 | doi:10.1038/nature07733
Association of reactive oxygen species levels and radioresistance in cancer stem cells
Maximilian Diehn1,2,12, Robert W. Cho2,3,12, Neethan A. Lobo2, Tomer Kalisky8, Mary Jo Dorie1, Angela N. Kulp2, Dalong Qian2, Jessica S. Lam2, Laurie E. Ailles2, Manzhi Wong2, Benzion Joshua4, Michael J. Kaplan4, Irene Wapnir5, Fred Dirbas5, George Somlo9, Carlos Garberoglio10, Benjamin Paz10, Jeannie Shen10, Sean K. Lau11, Stephen R. Quake8, J. Martin Brown1, Irving L. Weissman2,6 & Michael F. Clarke2,7
1 Department of Radiation Oncology,
2 Stanford Institute for Stem Cell Biology and Regenerative Medicine,
3 Department of Pediatrics Division of Stem Cell Transplantation,
4 Department of Otolaryngology—Head and Neck Surgery,
5 Department of Surgery,
6 Departments of Pathology and Developmental Biology,
7 Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA
8 Department of Bioengineering and Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA
9 Department of Medical Oncology and Therapeutics Research,
10 Department of Surgery,
11 Department of Pathology, City of Hope National Medical Center, Duarte, California, California 91010, USA
12 These authors contributed equally to this work.
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.
