Driessens Gregory
Université Libre de Bruxelles, IRIBHM.
Crit Rev Oncog. 2014;19(5):317-25. doi: 10.1615/critrevoncog.2014011770.
One of the key goals of cancer research is to understand more precisely the mechanisms of tumor growth. It has been hypothesized for several decades that some tumors may be hierarchically organized as normal tissues. Many studies have suggested the existence of cancer stem cells (CSCs) at the top of the cellular hierarchy in tumors. The proof of concept for the existence of the CSC model has been demonstrated by the ability of particular tumor cells to reform tumor growth upon transplantation into severely immunodeficient mice. CSCs have been described in many different human cancers and have been hypothesized to sustain tumor growth, to resist chemo- and radiotherapy, and to be responsible for tumor relapse. While these studies clearly show the differential potential of cancer cells in these experimental conditions and demonstrate functional intratumoral heterogeneity, they do not necessarily reflect the actual fate of tumor cells in their native environment; the existence of CSCs during unperturbed tumor growth remained unproven for a long time. Different recent reports used clonal analysis and lineage tracing tools to demonstrate the hierarchical organization of tumors in vivo in unperturbed colon and skin cancer models. This review discusses the unique opportunities opened through the use of tracing methods to further characterize CSCs in different tumor models as well as their utility in dissecting the mechanism of action of new therapeutics targeting specifically CSCs.
癌症研究的关键目标之一是更精确地了解肿瘤生长的机制。几十年来，人们一直假设某些肿瘤可能像正常组织一样具有层级结构。许多研究表明，肿瘤细胞层级结构顶端存在癌症干细胞（CSC）。特定肿瘤细胞移植到严重免疫缺陷小鼠体内后能够重新形成肿瘤生长，这一现象证明了CSC模型存在的概念。在许多不同的人类癌症中都发现了CSC，并且据推测它们能够维持肿瘤生长、抵抗化疗和放疗，并导致肿瘤复发。虽然这些研究清楚地显示了癌细胞在这些实验条件下的不同潜能，并证明了肿瘤内功能异质性，但它们不一定能反映肿瘤细胞在其天然环境中的实际命运；在很长一段时间里，未受干扰的肿瘤生长过程中CSC的存在一直未得到证实。最近不同的报告使用克隆分析和谱系追踪工具，在未受干扰的结肠癌和皮肤癌模型中证明了肿瘤在体内的层级结构。本综述讨论了通过使用追踪方法为进一步表征不同肿瘤模型中的CSC所带来的独特机遇，以及这些方法在剖析专门针对CSC的新疗法作用机制方面的效用。
