Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research
Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research
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DOI：
10.1093/annonc/mdu018
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发表时间：
2014-08-01
影响因子：
50.5
通讯作者：
Hardingham, J. E.
中科院分区：
文献类型：
--
作者：
Grover, P. K.;Cummins, A. G.;Hardingham, J. E.
越来越多的证据表明，循环肿瘤细胞（CTC）是转移性复发的原因，这激发了人们对其检测和定量的兴趣。尽管已经开发了许多方法用于CTC的富集和检测，但还没有一种达到“金”标准。由于基于上皮细胞粘附分子（EpCAM）的CTC富集提供了几个优点，因此它是最常用的方法之一，并已适用于高通量技术。然而，新出现的证据表明CTC是高度异质性的：它们由上皮肿瘤细胞、上皮-间充质转化（EMT）细胞、杂交（上皮/EMT+）肿瘤细胞、不可逆EMT+肿瘤细胞和循环肿瘤干细胞（CTSC）组成。基于EpCAM的方法不能检测表达低水平EpCAM的CTC和非上皮表型，例如CTSC和已经经历EMT并且不再表达EpCAM的那些。因此，该方法可能导致低估了CTC，特别是CTSC和EMT+肿瘤细胞在癌症传播中的重要性。在这里，我们提供了一个关键的审查研究文献的概念不断演变的CTC和他们的富集不足的EpCAM为基础的技术和临床癌症研究。审查还概述了该领域的未来前景。
Increasing evidence suggests that circulating tumour cells (CTCs) are responsible for metastatic relapse and this has fuelled interest in their detection and quantification. Although numerous methods have been developed for the enrichment and detection of CTCs, none has yet reached the 'gold' standard. Since epithelial cell adhesion molecule (EpCAM)-based enrichment of CTCs offers several advantages, it is one of the most commonly used and has been adapted for high-throughput technology. However, emerging evidence suggests that CTCs are highly heterogeneous: they consist of epithelial tumour cells, epithelial-to-mesenchymal transition (EMT) cells, hybrid (epithelial/EMT+) tumour cells, irreversible EMT+ tumour cells, and circulating tumour stem cells (CTSCs). The EpCAM-based approach does not detect CTCs expressing low levels of EpCAM and non-epithelial phenotypes such as CTSCs and those that have undergone EMT and no longer express EpCAM. Thus, the approach may lead to underestimation of the significance of CTCs, in general, and CTSCs and EMT+ tumour cells, in particular, in cancer dissemination. Here, we provide a critical review of research literature on the evolving concept of CTCs and the inadequacy of their enrichment by EpCAM-based technology for basic and clinical cancer research. The review also outlines future perspectives in the field.