Castro-Giner Francesc, Scheidmann Manuel C, Aceto Nicola
Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel, University Hospital Basel, Basel, Switzerland.
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Front Med (Lausanne). 2018 Feb 19;5:34. doi: 10.3389/fmed.2018.00034. eCollection 2018.
Circulating tumor cells (CTCs) are defined as those cells that detach from a cancerous lesion and enter the bloodstream. While generally most CTCs are subjected to high shear stress, anoikis signals, and immune attack in the circulatory system, few are able to survive and reach a distant organ in a viable state, possibly leading to metastasis formation. A large number of studies, both prospective and retrospective, have highlighted the association between CTC abundance and bad prognosis in patients with various cancer types. Yet, beyond CTC enumeration, much less is known about the distinction between metastatic and nonmetastatic CTCs, namely those features that enable only some CTCs to survive and seed a cancerous lesion at a distant site. In addition, critical aspects such as CTC heterogeneity, mechanisms that trigger CTC intravasation and extravasation, as well as vulnerabilities of metastatic CTCs subpopulations are poorly understood. In this short review, we highlight recent studies that successfully adopted functional and computational analysis to gain insights into CTC biology. We also discuss approaches to overcome challenges that are associated with CTC isolation, molecular and computational analysis, and speculate regarding few open questions that currently frame the CTC research field.
循环肿瘤细胞（CTCs）被定义为那些从癌性病变脱离并进入血液循环的细胞。虽然一般来说，大多数循环肿瘤细胞在循环系统中会受到高剪切应力、失巢凋亡信号和免疫攻击，但只有少数能够存活并以存活状态到达远处器官，这可能导致转移灶的形成。大量前瞻性和回顾性研究都强调了循环肿瘤细胞丰度与各种癌症类型患者不良预后之间的关联。然而，除了循环肿瘤细胞计数外，对于转移性和非转移性循环肿瘤细胞之间的区别，即那些仅使某些循环肿瘤细胞能够存活并在远处部位形成癌性病变的特征，人们了解得更少。此外，诸如循环肿瘤细胞异质性、触发循环肿瘤细胞内渗和外渗的机制以及转移性循环肿瘤细胞亚群的脆弱性等关键方面也知之甚少。在这篇简短的综述中，我们重点介绍了最近成功采用功能和计算分析来深入了解循环肿瘤细胞生物学的研究。我们还讨论了克服与循环肿瘤细胞分离、分子和计算分析相关挑战的方法，并对目前构成循环肿瘤细胞研究领域的一些未解决问题进行了推测。
