Baumann Michael, Krause Mechthild, Thames Howard, Trott Klaus, Zips Daniel
Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitt Dresden, Germany.
Int J Radiat Biol. 2009 May;85(5):391-402. doi: 10.1080/09553000902836404.
The present work summarises the history and current status of research into the importance of cancer stem cells for radiobiological research and for clinical radiation oncology. An effort is made to differentiate clonogenicity from stemness of cancer cells.
In radiooncology, cancer stem cells have been an important research field for five decades. Quantitative transplantation assays with evaluation of the take dose 50% (TD50) remain the gold standard to verify the stemness of the selected cells. New technologies allow sorting of tumour cells according to their surface marker expression and thereby selecting subpopulations that are enriched in cancer stem cells (e.g., CD133, CD44, CD29). While development of surface-marker-based assays is a highly important step in cancer-stem-cell research, to date there are still problems to be solved, e.g., the specifity of markers, adequate animal models, and optimised in vitro assays. Of special concern for radiobiology is that clonogenic in vitro assays do not necessarily measure stemness of cancer cells. This hampers investigations into the important question of whether cancer stem cells are more radioresistant than non-stem cells. The most extensive of the limited data on this topic relate to glioma stem cells identified by the surface marker CD133. These do not provide firm evidence for difference of radiosensitivity between stem and non stem cells. In spite of many problems to be solved, the combination of stem cell markers with radiobiological assays bears considerable promise for advancing translational research in radiation oncology.
本研究总结了癌症干细胞在放射生物学研究和临床放射肿瘤学中的重要性的研究历史和现状。努力区分癌细胞的克隆形成能力与干性。
在放射肿瘤学中，癌症干细胞已经成为一个重要的研究领域达五十年之久。通过评估半数接种剂量（TD50）的定量移植试验仍然是验证所选细胞干性的金标准。新技术允许根据肿瘤细胞的表面标志物表达进行分选，从而选择富含癌症干细胞的亚群（例如，CD133、CD44、CD29）。虽然基于表面标志物的检测方法的开发是癌症干细胞研究中非常重要的一步，但迄今为止仍有一些问题有待解决，例如标志物的特异性、合适的动物模型以及优化的体外检测方法。放射生物学特别关注的是，体外克隆形成试验不一定能测量癌细胞的干性。这阻碍了对癌症干细胞是否比非干细胞更具放射抗性这一重要问题的研究。关于这一主题的有限数据中，最广泛的是与通过表面标志物CD133鉴定的胶质瘤干细胞有关。这些数据并未提供干细胞与非干细胞之间放射敏感性差异的确凿证据。尽管有许多问题有待解决，但干细胞标志物与放射生物学检测方法的结合在推进放射肿瘤学的转化研究方面具有很大的前景。
