斯坦福大學干細胞生物學和再生醫(yī)學研究所,，放射腫瘤治療研究中心，兒科干細胞移植分部,，霍華休斯醫(yī)學研究所生物工程系等處的研究人員找出了癌癥干細胞中活性氧簇水平與抗輻射性的內在關聯(lián),，相關成果公布在最新一期的Nature上。
氧是人類生存必不可少的物質,，但是在氧氣的代謝過程中可能產生一種名為“活性氧簇”的物質,，這一類物質對人體絲毫沒有好處，它常常與癌癥,、心血管疾病以及老化有著千絲萬縷的關系,。
近期的研究發(fā)現(xiàn)，中樞神經(jīng)細胞干細胞,，造血干細胞和早期的其他祖細胞成熟前所含的“活性氧簇”水平比成熟后要低,，據(jù)說，這一差別對維持干細胞的功能具有關鍵的意義,。研究者推測,，上皮組織干細胞與上皮組織癌癥干細胞可能也具有類似的特征。以乳房上皮細胞為例,，研究者發(fā)現(xiàn),，乳房上皮細胞成熟前的活性氧簇的含量比成熟后低。值得關注的是,，人類和鼠類的乳腺癌干細胞亞群細胞比正常細胞的活性氧簇的含量低,。
研究小組發(fā)現(xiàn)，低水平的活性氧簇有助癌癥干細胞表達自由基清除系統(tǒng),。從藥理學意義上來說,，缺失活性氧簇的清除系統(tǒng)癌癥干細胞的集落生成能力降低，導致癌癥干細胞對輻射敏感,。這些研究結果表明,，部分癌癥干細胞的亞細胞群與正常的組織干細胞相似，含有低水平的活性氧簇，與非致瘤性的祖細胞相比,，這些細胞清除自由基的能力更強,，這也可能是腫瘤細胞對輻射產生耐受性的一個機制。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
