INSERM U1035, Université de Bordeaux, 33000 Bordeaux, France.
Centre Hospitalier Universitaire (CHU) de Bordeaux, 33000 Bordeaux, France.
Int J Mol Sci. 2020 Apr 10;21(7):2653. doi: 10.3390/ijms21072653.
The presence of circulating tumor cells (CTCs) and CTC clusters, also known as tumor microemboli, in biological fluids has long been described. Intensive research on single CTCs has made a significant contribution in understanding tumor invasion, metastasis tropism, and intra-tumor heterogeneity. Moreover, their being minimally invasive biomarkers has positioned them for diagnosis, prognosis, and recurrence monitoring tools. Initially, CTC clusters were out of focus, but major recent advances in the knowledge of their biogenesis and dissemination reposition them as critical actors in the pathophysiology of cancer, especially metastasis. Increasing evidence suggests that "united" CTCs, organized in clusters, resist better and carry stronger metastatic capacities than "divided" single CTCs. This review gathers recent insight on CTC cluster origin and dissemination. We will focus on their distinct molecular package necessary to resist multiple cell deaths that all circulating cells normally face. We will describe the molecular basis of their increased metastatic potential as compared to single CTCs. We will consider their clinical relevance as prognostic biomarkers. Finally, we will propose future directions for research and clinical applications in this promising topic in cancer.
循环肿瘤细胞 (CTC) 和 CTC 簇（也称为肿瘤微栓子）在生物体液中的存在很早就有描述。对单个 CTC 的深入研究对理解肿瘤侵袭、转移趋向性和肿瘤内异质性做出了重大贡献。此外，它们作为微创生物标志物，被定位为用于诊断、预后和复发监测的工具。最初，CTC 簇并不受关注，但最近在其发生和传播的知识方面取得的重大进展，使它们重新成为癌症病理生理学，尤其是转移的关键因素。越来越多的证据表明，组织成簇的“联合”CTC 比“分裂”的单个 CTC 更能抵抗并具有更强的转移能力。这篇综述汇集了关于 CTC 簇起源和传播的最新见解。我们将重点关注它们抵抗所有循环细胞正常面临的多种细胞死亡所需的独特分子包装。我们将描述与单个 CTC 相比，它们增强转移潜能的分子基础。我们将考虑它们作为预后生物标志物的临床相关性。最后，我们将为这一癌症领域有前途的课题提出未来的研究和临床应用方向。
