文章：

将干细胞生物学原理应用于癌症

Applying the principles of stem-cell biology to cancer

原文发布日期：2003-12-01

DOI: 10.1038/nrc1232

类型: Review Article

开放获取: 否

要点：

1. Not all cancer cells are created equal. There are intrinsic differences among cancer cells from the same patient in terms of their ability to proliferate and form tumours in vivo.
2. A subset of cancer cells have the properties of cancer stem cells, which self-renew to generate additional cancer stem cells and differentiate to generate phenotypically diverse cancer cells with limited proliferative potential. Cancer stem cells are highly enriched for the ability to form tumours following transplantation relative to bulk tumour cells or non-tumorigenic cancer cells.
3. Cancer stem cells have been characterized in the context of human acute myeloid leukaemia, breast cancer and glioblastoma. In each case, surface markers have been identified that distinguish cancer stem cells from cancer cells with more limited proliferative potential, allowing the prospective identification of cancer stem cells.
4. In some cases, cancer stem cells might arise from the mutational transformation of normal stem cells, whereas in other cases mutations might cause restricted progenitors or differentiated cells to acquire properties of cancer stem cells such as self-renewal potential.
5. The neoplastic proliferation of cancer stem cells is likely to be driven by mutations that inappropriately activate pathways that promote the self-renewal of normal stem cells. Examples of these pathways include the WNT, and BMI1-dependent pathways that regulate the self-renewal of haematopoietic stem cells and neural stem cells.
6. Further characterization of cancer stem cells might lead to improved diagnostics and therapies by allowing us to better identify and target cancer stem cells. To cure cancer it is necessary to kill, differentiate or prevent the metastasis of cancer stem cells.

要点翻译：

1. 并非所有癌细胞生而平等。同一患者体内的癌细胞在增殖和体内成瘤能力方面存在内在差异。
2. 一部分癌细胞具有癌症干细胞特性，它们可通过自我更新产生更多癌症干细胞，并通过分化形成表型多样、增殖潜能有限的癌细胞。与整体肿瘤细胞或非致瘤性癌细胞相比，癌症干细胞在移植后形成肿瘤的能力高度富集。
3. 癌症干细胞已在人类急性髓系白血病、乳腺癌和胶质母细胞瘤中得到鉴定。每种病例中均发现可区分癌症干细胞与增殖潜能有限癌细胞的表面标志物，从而实现对癌症干细胞的前瞻性识别。
4. 在某些情况下，癌症干细胞可能源于正常干细胞的突变转化；而在其他情况下，突变可能导致受限祖细胞或分化细胞获得癌症干细胞特性（如自我更新能力）。
5. 癌症干细胞的肿瘤性增殖很可能由异常激活正常干细胞自我更新通路的突变驱动。例如调控造血干细胞和神经干细胞自我更新的WNT通路及BMI1依赖性通路。
6. 对癌症干细胞的进一步表征将有助于我们更精准地识别和靶向这些细胞，从而改善诊断和治疗方法。根治癌症需要清除、分化或阻止癌症干细胞的转移。

英文摘要：

Why are tumours heterogeneous, in terms of cell phenotype and proliferative potential, even in cases in which all cells are derived from a single clone? Ongoing mutagenesis can partially explain this heterogeneity, but it also seems that some tumours arise from small populations of 'cancer stem cells' that give rise to phenotypically diverse cancer cells, with less proliferative potential. These cancer stem cells are likely to arise from mutations that dysregulate normal stem-cell self-renewal. Using this information, it might be possible to devise more effective therapies.

摘要翻译： 

为何即使所有细胞均源自同一克隆，肿瘤在细胞表型及增殖潜能方面仍呈异质性？持续突变可在一定程度上解释这种差异，但似乎某些肿瘤还源于少量“癌症干细胞”，这些细胞能产生表型多样且增殖潜能较低的癌细胞。癌症干细胞可能由调控正常干细胞自我更新的基因发生突变而形成。利用这一信息，有望设计出更有效的治疗方案。

原文链接：

Applying the principles of stem-cell biology to cancer