文章：

实体肿瘤中的癌症干细胞：积累证据和未解决的问题

Cancer stem cells in solid tumours: accumulating evidence and unresolved questions

原文发布日期：2008-09-11

DOI: 10.1038/nrc2499

类型: Review Article

开放获取: 否

要点：

1. The cancer stem cell (CSC) hypothesis is an attractive model to account for the functional heterogeneity that is commonly observed in solid tumours. It proposes a hierarchical organization of cells within the tumour, in which a subpopulation of stem-like cells is responsible for sustaining tumour growth.
2. The first evidence for CSCs came from acute myeloid leukaemia. There is now increasing evidence for CSCs in a variety of solid tumours (both mouse and human), provided through transplantation studies using prospectively isolated tumour cells.
3. The frequency of CSCs in solid tumours is highly variable, reflecting biological variation as well as technical issues. Technical issues include the purity of solid tumour cell fractionation, the requirement for more definitive markers and the challenges associated with xenotransplantation. Ultimately it will be necessary to study CSCs and potential heterogeneity within this population at a clonal level through 'cell tagging'.
4. Not all solid tumours will follow the CSC model of heterogeneity. Some may conform to the clonal evolution model, in which a dominant population of proliferating cells drives tumorigenesis.
5. Metastatic CSCs may exist, with properties distinct from primary CSCs.
6. The concept of CSCs has significant clinical implications: CSCs have been shown to be more resistant to chemotherapy and radiotherapy.
7. Recent reports, primarily for haematopoietic malignancies, suggest that CSCs can be selectively targeted without ablating normal stem cell function.

要点翻译：

1. 癌症干细胞（CSC）假说是一个颇具吸引力的模型，用以解释实体瘤中常见的功能异质性现象。该假说提出肿瘤内部细胞存在层级结构，其中具有干细胞特性的亚群负责维持肿瘤的生长。
2. CSC的首个证据来自急性髓系白血病。目前通过前瞻性分离肿瘤细胞的移植研究，越来越多证据表明多种实体瘤（包括小鼠和人类）中存在CSC。
3. 实体瘤中CSC的出现频率存在显著差异，这既反映了生物学变异，也涉及技术问题。技术问题包括实体瘤细胞分馏的纯度、对更明确标志物的需求，以及异种移植相关的挑战。最终需要通过“细胞标记”技术在克隆水平研究CSC及其潜在异质性。
4. 并非所有实体瘤都遵循CSC异质性模型。有些肿瘤可能符合克隆进化模型，即由占主导地位的增殖细胞群驱动肿瘤发生。
5. 可能存在转移性CSC，其特性与原发CSC不同。
6. CSC概念具有重要临床意义：研究表明CSC对化疗和放疗具有更强耐药性。
7. 最新研究（主要针对造血系统恶性肿瘤）表明，可以在不损伤正常干细胞功能的前提下选择性靶向CSC。

英文摘要：

Solid tumours are an enormous cancer burden and a major therapeutic challenge. The cancer stem cell (CSC) hypothesis provides an attractive cellular mechanism to account for the therapeutic refractoriness and dormant behaviour exhibited by many of these tumours. There is increasing evidence that diverse solid tumours are hierarchically organized and sustained by a distinct subpopulation of CSCs. Direct evidence for the CSC hypothesis has recently emerged from mouse models of epithelial tumorigenesis, although alternative models of heterogeneity also seem to apply. The clinical relevance of CSCs remains a fundamental issue but preliminary findings indicate that specific targeting may be possible.

摘要翻译： 

实体肿瘤是巨大的癌症负担，也是重大的治疗挑战。癌症干细胞（CSC）假说提供了一个有吸引力的细胞机制，用以解释许多这些肿瘤表现出的治疗耐药性和休眠行为。越来越多的证据表明，多种实体肿瘤具有层级结构，并由一个独特的CSC亚群维持。来自小鼠上皮肿瘤发生模型的研究最近为CSC假说提供了直接证据，尽管异质性的替代模型似乎也适用。CSC的临床相关性仍是一个基本问题，但初步研究结果表明，特异性靶向可能是可行的。

原文链接：

Cancer stem cells in solid tumours: accumulating evidence and unresolved questions