Defining the mode of tumour growth by clonal analysis.
Defining the mode of tumour growth by clonal analysis.
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DOI：
10.1038/nature11344
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发表时间：
2012-08-23
期刊：
影响因子：
64.8
通讯作者：
Blanpain C
中科院分区：
文献类型：
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作者：
Driessens G;Beck B;Caauwe A;Simons BD;Blanpain C
最近的研究采用分离肿瘤细胞亚群，然后将其移植到免疫缺陷小鼠体内的方法，提供证据表明，某些肿瘤，包括鳞状皮肤肿瘤，含有具有高克隆潜能的细胞，这些细胞被称为癌症干细胞（CSCs）。到目前为止，CSC的特性仅通过移植试验进行了研究，它们在未受干扰的肿瘤生长中的存在尚未得到证实。在这里，我们利用克隆分析鳞状皮肤肿瘤使用遗传谱系追踪解开肿瘤生长模式在其原生环境的体内。为此，我们使用了一种基因标记策略，该策略允许在肿瘤进展的不同阶段对单个肿瘤细胞进行标记和追踪。令人惊讶的是，我们发现良性乳头状瘤中的大多数标记肿瘤细胞只有有限的增殖潜力，而一小部分具有长期存在的能力，从而产生占据肿瘤很大一部分的后代。除了证实乳头状瘤中存在两个不同的增殖细胞区室，反映了正常组织的组成、层次和命运行为外，克隆命运数据的定量分析表明，更持久的群体具有干细胞样特征，并且每天循环两次，而第二次代表周期较慢的短暂群体，产生最终分化的肿瘤细胞。这种行为被证明与双标记实验和详细的克隆命运特征一致。相比之下，侵袭性鳞状细胞癌的克隆大小和增殖潜力的测量显示出不同的行为模式，与单个CSC群体的几何扩张相一致，最终分化的潜力有限。本研究提供了第一个实验证据，证明在稳定的实体瘤生长过程中存在csc。
Recent studies using the isolation of a subpopulation of tumour cells followed by their transplantation into immunodeficient mice provide evidence that certain tumours, including squamous skin tumours, contain cells with high clonogenic potential that have been referred to as cancer stem cells (CSCs). Until now, CSC properties have only been investigated by transplantation assays, and their existence in unperturbed tumour growth is unproven. Here we make use of clonal analysis of squamous skin tumours using genetic lineage tracing to unravel the mode of tumour growth in vivo in its native environment. To this end, we used a genetic labelling strategy that allows individual tumour cells to be marked and traced over time at different stages of tumour progression. Surprisingly, we found that the majority of labelled tumour cells in benign papilloma have only limited proliferative potential, whereas a fraction has the capacity to persist long term, giving rise to progeny that occupy a significant part of the tumour. As well as confirming the presence of two distinct proliferative cell compartments within the papilloma, mirroring the composition, hierarchy and fate behaviour of normal tissue, quantitative analysis of clonal fate data indicates that the more persistent population has stemcell-like characteristics and cycles twice per day, whereas the second represents a slower cycling transient population that gives rise to terminally differentiated tumour cells. Such behaviour is shown to be consistent with double-labelling experiments and detailed clonal fate characteristics. By contrast, measurements of clone size and proliferative potential in invasive squamous cell carcinoma show a different pattern of behaviour, consistent with geometric expansion of a single CSC population with limited potential for terminal differentiation. This study presents the first experimental evidence for the existence of CSCs during unperturbed solid tumour growth.
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影响因子：
64.8
作者：
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通讯作者：
Maley, Carlo C.
影响因子：
78.5
作者：
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通讯作者：
Klein, Christoph A.
影响因子：
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作者：
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DOI：
10.1073/pnas.1107807108
发表时间：
2011-06-28
影响因子：
11.1
作者：
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通讯作者：
Fuchs, Elaine
影响因子：
14.8
作者：
通讯作者：
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