Yadav Priya, Rajendrasozhan Saravanan, Lajimi Ramzi Hadj, Patel Raja Ramadevi, Heymann Dominique, Prasad N Rajendra
Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, Tamil Nadu, India.
Department of Chemistry, College of Science, University of Ha'il, Ha'il, Saudi Arabia.
Front Oncol. 2025 Apr 7;15:1494723. doi: 10.3389/fonc.2025.1494723. eCollection 2025.
Circulating tumor cells (CTCs) are cancerous cells that extravasate from the primary tumor or metastatic foci and travel through the bloodstream to distant organs. CTCs provide crucial insights into cancer metastasis, the evolution of tumor genotypes during treatment, and the development of chemo- and/or radio-resistance during disease progression. The process of Epithelial-to-mesenchymal transition (EMT) plays a key role in CTCs formation, as this process enhances cell's migration properties and is often associated with increased invasiveness thereby leading to chemotherapy resistance. During the EMT process, tumor cells lose epithelial markers like EpCAM and acquire mesenchymal markers such as vimentin driven by transcription factors like Snail and Twist. CTCs are typically identified using specific cell surface markers, which vary depending on the cancer type. Common markers include EpCAM, used for epithelial cancers; CD44 and CD24, which are associated with cancer stem cells; and cytokeratins, such as CK8 and CK18. Other markers like HER2/neu and vimentin can also be used to target CTCs in specific cancer types and stages. Commonly, immune-based isolation techniques are being implemented for the isolation and enrichment of CTCs. This review emphasizes the clinical relevance of CTCs, particularly in understanding drug resistance mechanisms, and underscores the importance of EMT-derived CTCs in multidrug resistance (MDR). Moreover, the review also discusses CTCs-specific surface markers that are crucial for their isolation and enrichment. Ultimately, the EMT-specific markers found in CTCs could provide significant information to halt the disease progression and enable personalized therapies.
循环肿瘤细胞（CTCs）是从原发性肿瘤或转移灶渗出并通过血液循环转移至远处器官的癌细胞。CTCs为癌症转移、治疗期间肿瘤基因型的演变以及疾病进展过程中化疗和/或放疗耐药性的发展提供了关键见解。上皮-间质转化（EMT）过程在CTCs形成中起关键作用，因为该过程增强了细胞的迁移特性，并且通常与侵袭性增加相关，从而导致化疗耐药。在EMT过程中，肿瘤细胞失去上皮标志物如EpCAM，并获得间质标志物如波形蛋白，这一过程由转录因子如Snail和Twist驱动。CTCs通常使用特定的细胞表面标志物来识别，这些标志物因癌症类型而异。常见的标志物包括用于上皮癌的EpCAM；与癌症干细胞相关的CD44和CD24；以及细胞角蛋白，如CK8和CK18。其他标志物如HER2/neu和波形蛋白也可用于在特定癌症类型和阶段靶向CTCs。通常，基于免疫的分离技术被用于CTCs的分离和富集。本综述强调了CTCs的临床相关性，特别是在理解耐药机制方面，并强调了EMT衍生的CTCs在多药耐药（MDR）中的重要性。此外，该综述还讨论了对CTCs的分离和富集至关重要的CTCs特异性表面标志物。最终，在CTCs中发现的EMT特异性标志物可为阻止疾病进展和实现个性化治疗提供重要信息。
