Nature：癌症干细胞研究新热点

时间：2009年2月6日

来源：Nature

编辑推荐：

生物通报道，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。

文章的通讯作者是Michael F. Clarke教授早年毕业于美国印第安大大学，现任斯坦福大学干细胞与再生医学研究所的副主任，Michael F. Clarke教授主要研究领域包括两方面，其一：干细胞的自我更新能力以及癌变的细胞的复制过程，其二是，鉴定和研究癌症干细胞的特征。

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。（生物通小茜）

生物通推荐原文摘要：Association of reactive oxygen species levels and radioresistance in cancer stem cells

【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.（生物通）

Michael F. Clarke代表性文章：

Akala OO, Park IK, Qian D, Pihalja M, Becker MW, Clarke MF "Long-term haematopoietic reconstitution by Trp53(-)(/-)p16(Ink4a)(-/-)p19(Arf-)(/-) multipotent progenitors." Nature 2008;

Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K, Clarke MF "The prognostic role of a gene signature from tumorigenic breast-cancer cells." N Engl J Med 2007; 356: 3: 217-26

Clarke MF, Fuller M "Stem cells and cancer: two faces of eve." Cell 2006; 124: 6: 1111-5 More »

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF "Prospective identification of tumorigenic breast cancer cells." Proc Natl Acad Sci U S A 2003; 100: 7: 3983-8

Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ, Clarke MF "Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells." Nature 2003; 423: 6937: 302-5