Alix-Panabières Catherine, Mader Sonja, Pantel Klaus
Laboratory of Rare Human Circulating Cells (LCCRH), Department of Cellular and Tissular Biopathology of Tumors, University Medical Centre, 641, avenue du Doyen Gaston Giraud, 34093, Montpellier Cedex 5, France.
EA2415 - Help for Personalized Decision: Methodological Aspects, University Institute of Clinical Research (IURC), Montpellier University, Montpellier, France.
J Mol Med (Berl). 2017 Feb;95(2):133-142. doi: 10.1007/s00109-016-1500-6. Epub 2016 Dec 24.
Epithelial-to-Mesenchymal Transition (EMT) is a complex process that supports the migratory capacity of epithelial tumor cells and is thought to play a crucial role in promoting cancer metastasis. Despite the wealth of experimental data, the exact role of EMT in cancer patients remains more controversial. Over the past 10 years, sensitive technologies that allow the detection and molecular characterization of circulating tumor cells (CTCs) in the peripheral blood of tumor patients have been developed. These analyses help to shed new light into the importance of EMT for human tumor cell dissemination. CTCs with mesenchymal features can be attributed in some clinical studies (in particularly on breast cancer) to higher disease stages, presence of metastases, and even to therapy response and worse outcome. However, the published studies addressing the impact of mesenchymal-like CTCs show heterogeneity with regard to assay specificity, size of cancer and control groups, and endpoint parameters. In the present review, we present the key features of the biology of CTCs in relation to epithelial-to-mesenchy-mal plasticity, describe the current technologies for enrichment and detection of CTCs with high epithelial-mesenchymal plasticity, and discuss the clinical studies that have assessed the relevance of mesenchymal CTCs in carcinoma patients.
上皮-间质转化(EMT)是一个复杂的过程,它增强上皮肿瘤细胞的迁移能力,并被认为在促进癌症转移中起关键作用。尽管有大量实验数据,但EMT在癌症患者中的确切作用仍存在更多争议。在过去10年里,已开发出能检测肿瘤患者外周血中循环肿瘤细胞(CTC)并对其进行分子特征分析的灵敏技术。这些分析有助于进一步了解EMT对人类肿瘤细胞播散的重要性。在一些临床研究中(尤其是针对乳腺癌的研究),具有间质特征的CTC与更高的疾病分期、转移灶的存在、甚至与治疗反应及更差的预后相关。然而,已发表的关于间充质样CTC影响的研究在检测特异性、癌症及对照组规模和终点参数方面存在异质性。在本综述中,我们阐述了与上皮-间质可塑性相关的CTC生物学关键特征,描述了当前用于富集和检测具有高上皮-间质可塑性的CTC的技术,并讨论了评估间质CTC在癌症患者中相关性的临床研究。