Division of General Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Clin Cancer Res. 2010 Jun 15;16(12):3113-20. doi: 10.1158/1078-0432.CCR-09-2824. Epub 2010 Jun 8.
The cancer stem cell (CSC) or cancer-initiating cancer (C-IC) model has garnered considerable attention over the past several years since Dick and colleagues published a seminal report showing that a hierarchy exists among leukemic cells. In more recent years, a similar hierarchical organization, at the apex of which exists the CSC, has been identified in a variety of solid tumors. Human CSCs are defined by their ability to: (i) generate a xenograft that histologically resembles the parent tumor from which it was derived, (ii) be serially transplanted in a xenograft assay thereby showing the ability to self-renew (regenerate), and (iii) generate daughter cells that possess some proliferative capacity but are unable to initiate or maintain the cancer because they lack intrinsic regenerative potential. The emerging complexity of the CSC phenotype and function is at times daunting and has led to some confusion in the field. However, at its core, the CSC model is about identifying and characterizing the cancer cells that possess the greatest capacity to regenerate all aspects of the tumor. It is becoming clear that cancer cells evolve as a result of their ability to hijack normal self-renewal pathways, a process that can drive malignant transformation. Studying self-renewal in the context of cancer and CSC maintenance will lead to a better understanding of the mechanisms driving tumor growth. This review will address some of the main controversies in the CSC field and emphasize the importance of focusing first and foremost on the defining feature of CSCs: dysregulated self-renewal capacity.
过去几年，由于 Dick 及其同事发表了一篇开创性的报告，表明白血病细胞中存在一个层次结构，癌症干细胞（CSC）或起始性癌症（C-IC）模型引起了相当大的关注。近年来，在各种实体瘤中也发现了类似的层次组织，其顶端存在 CSC。人类 CSC 的定义特征是：（i）生成在组织学上与源自其的亲本肿瘤相似的异种移植物，（ii）在异种移植测定中连续移植从而显示自我更新（再生）的能力，以及（iii）生成具有一定增殖能力但不能起始或维持癌症的子细胞，因为它们缺乏内在的再生潜能。CSC 表型和功能的新兴复杂性有时令人望而却步，并导致该领域出现一些混乱。然而，其核心是确定和表征具有最大能力再生肿瘤所有方面的癌症细胞。越来越明显的是，癌细胞由于能够劫持正常的自我更新途径而进化，这一过程可驱动恶性转化。在癌症和 CSC 维持的背景下研究自我更新将有助于更好地理解驱动肿瘤生长的机制。这篇综述将讨论 CSC 领域的一些主要争议，并强调首先关注 CSC 的定义特征：失调的自我更新能力的重要性。
