Cheng Le, Ramesh Anirudh V, Flesken-Nikitin Andrea, Choi Jinhyang, Nikitin Alexander Yu
Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
Toxicol Pathol. 2010 Jan;38(1):62-71. doi: 10.1177/0192623309354109. Epub 2009 Nov 17.
The cancer stem cell concept assumes that cancers are mainly sustained by a small pool of neoplastic cells, known as cancer stem cells or tumor initiating cells, which are able to reproduce themselves and produce phenotypically heterogeneous cells with lesser tumorigenic potential. Cancer stem cells represent an appealing target for development of more selective and efficient therapies. However, direct testing of the cancer stem cell concept and assessment of its therapeutic implications in human cancers have been complicated by the use of immunocompromised mice. Genetically defined immunocompetent autochthonous mouse models of human cancer provide a valuable tool to address this problem. Furthermore, they allow for a better understanding of the relevance of mechanisms controlling normal stem cell compartment to carcinogenesis. Advantages and disadvantages of some of the existing mouse models are reviewed, and future challenges in cancer stem cell research are outlined.
癌症干细胞概念假定癌症主要由一小群肿瘤细胞维持,这些细胞被称为癌症干细胞或肿瘤起始细胞,它们能够自我复制并产生具有较低致瘤潜力的表型异质性细胞。癌症干细胞是开发更具选择性和高效性疗法的一个有吸引力的靶点。然而,使用免疫缺陷小鼠使得对癌症干细胞概念的直接测试及其在人类癌症中的治疗意义评估变得复杂。基因定义的人类癌症免疫健全的自发小鼠模型为解决这一问题提供了一个有价值的工具。此外,它们有助于更好地理解控制正常干细胞区室的机制与致癌作用的相关性。本文综述了一些现有小鼠模型的优缺点,并概述了癌症干细胞研究未来面临的挑战。