Adams Jerry M, Strasser Andreas
The Walter and Eliza Hall Institute of Medical Research Melbourne, Victoria, Australia.
Cancer Res. 2008 Jun 1;68(11):4018-21. doi: 10.1158/0008-5472.CAN-07-6334.
A key issue for cancer biology and therapy is whether the relentless growth of a tumor is driven by a substantial proportion of its cells or exclusively by a rare subpopulation, commonly termed "cancer stem cells." Support for the cancer stem cell model has been stimulated by experiments in which human tumor cells were transplanted into immunodeficient mice. Most notably, in human acute myeloid leukemia, only a minute proportion of the cells, displaying a defined phenotype, could seed leukemia in mice. Xenotransplantation, however, may fail to reveal many tumor growth-sustaining cells because the foreign microenvironment precludes essential interactions with support cells. In studies that instead have transplanted mouse leukemias and lymphomas into syngeneic animals, most of the tumors seem to be maintained by the dominant cell population, and only a few types of mouse leukemia seem to be sustained by a minor tumor growth-sustaining subpopulation. The collective evidence suggests that various tumors may span the spectrum between the extremes represented by the two models. If tumor growth can indeed be sustained either by rare cancer stem cells or dominant clones or both, as current evidence suggests, curative therapy for many types of tumors will most likely require targeting all the tumor cell populations.
癌症生物学与治疗的一个关键问题是，肿瘤的持续生长是由其大部分细胞驱动，还是仅由罕见的亚群（通常称为“癌症干细胞”）驱动。将人类肿瘤细胞移植到免疫缺陷小鼠体内的实验激发了对癌症干细胞模型的支持。最值得注意的是，在人类急性髓系白血病中，只有极小比例的具有特定表型的细胞能够在小鼠体内引发白血病。然而，异种移植可能无法揭示许多维持肿瘤生长的细胞，因为外来的微环境排除了与支持细胞的必要相互作用。在将小鼠白血病和淋巴瘤移植到同基因动物体内的研究中，大多数肿瘤似乎由占主导地位的细胞群体维持，只有少数类型的小鼠白血病似乎由一个较小的维持肿瘤生长的亚群维持。综合证据表明，各种肿瘤可能处于这两种模型所代表的极端情况之间的范围内。如果肿瘤生长确实可以由罕见的癌症干细胞或占主导地位的克隆或两者共同维持，正如目前的证据所表明的那样，那么对许多类型肿瘤的治愈性治疗很可能需要针对所有肿瘤细胞群体。
