Laboratory of Rare Human Circulating Cells (LCCRH), University Medical Centre of Montpellier, UPRES, EA2415, Montpellier, France.
Laboratory of Rare Human Circulating Cells (LCCRH), University Medical Centre of Montpellier, UPRES, EA2415, Montpellier, France.
Mol Aspects Med. 2020 Apr;72:100816. doi: 10.1016/j.mam.2019.07.008. Epub 2019 Aug 21.
Metastasis is the main cause of death in patients with cancer. The molecular mechanisms underlying the different metastasis steps are not yet fully known, partly because most studies have been focusing only on cancer cells within the tumor. Currently, with the development of technologies for the enrichment and capture of circulating tumor cells (CTCs), it is possible to characterize cancer cells at the exact moment of metastasis initiation. Therefore, CTCs are a promising bio-source for real-time liquid biopsies in patients with cancer. However, their exploitation has been hampered by the limited number of CTCs in the bloodstream and the changing phenotype of cancer cells during the metastatic process. Different methods have been developed to expand CTCs in vitro and in vivo (in animal models) with the aim of characterizing functional metastasis-initiator CTCs with stemness traits, and to obtain new diagnostics and therapeutic tools. In this review, we describe how the establishment of in vitro CTC cultures and of CTC-derived xenografts has led to the identification of molecular mechanisms related to metastasis initiation by CTCs, such as epithelial-to-mesenchymal transition (EMT), stemness, and clustering. These models enable the functional analysis and in-depth proteomic, transcriptomic and genomic profiling of metastasis-competent CTCs. We then discuss the relationship between EMT and stem cell features, and how these aspects might interact with other factors in the tumor microenvironment to induce CTC dissemination and proliferation in distant organs.
转移是癌症患者死亡的主要原因。不同转移步骤的分子机制尚不完全清楚，部分原因是大多数研究仅集中在肿瘤内的癌细胞上。目前，随着富集和捕获循环肿瘤细胞（CTC）技术的发展，有可能在转移起始的确切时刻对癌细胞进行特征描述。因此，CTC 是癌症患者实时液体活检的有前途的生物来源。然而，由于血液中 CTC 的数量有限，以及癌细胞在转移过程中的表型变化，其利用受到了阻碍。已经开发了不同的方法来在体外和体内（在动物模型中）扩增 CTC，目的是表征具有干性特征的功能性转移起始 CTC，并获得新的诊断和治疗工具。在这篇综述中，我们描述了体外 CTC 培养物和 CTC 衍生的异种移植物的建立如何导致鉴定与 CTC 起始转移相关的分子机制，例如上皮-间充质转化（EMT）、干性和聚类。这些模型能够对转移能力 CTC 进行功能分析和深入的蛋白质组学、转录组学和基因组分析。然后，我们讨论了 EMT 和干细胞特征之间的关系，以及这些方面如何与肿瘤微环境中的其他因素相互作用，以诱导 CTC 在远处器官的扩散和增殖。
