Jia Fei, Wang Yuehua, Fang Zhiguo, Dong Jierong, Shi Fanghao, Zhang Weikai, Wang Zihua, Hu Zhiyuan
CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Anal Chem. 2021 Apr 13;93(14):5670-5675. doi: 10.1021/acs.analchem.1c00577. Epub 2021 Mar 31.
The monitoring of circulating tumor cells (CTCs) has recently served as a promising approach for assessing prognosis and evaluating cancer treatment. We have already developed a CTCs enrichment platform by EpCAM recognition peptide-functionalized magnetic nanoparticles (EP@MNPs). However, considering heterogeneous CTCs generated through epithelial-mesenchymal transition (EMT), mesenchymal CTCs would be missed with this method. Notably, N-cadherin, overexpressed on mesenchymal CTCs, can facilitate the migration of cancer cells. Hence, we screened a novel peptide targeting N-cadherin, NP, and developed a new CTCs isolation approach via NP@MNPs to complement EpCAM methods' deficiencies. NP@MNPs had a high capture efficiency (about 85%) of mesenchymal CTCs from spiked human blood. Subsequently, CTCs were captured and sequenced at the single-cell level via NP@MNPs and EP@MNPs, RNA profiles of which showed that epithelial and mesenchymal subgroups could be distinguished. Here, a novel CTCs isolation platform laid the foundation for mesenchymal CTCs isolation and subsequent molecular analysis.
循环肿瘤细胞（CTCs）监测最近已成为评估预后和评价癌症治疗的一种有前景的方法。我们已经通过上皮细胞粘附分子（EpCAM）识别肽功能化磁性纳米颗粒（EP@MNPs）开发了一种CTCs富集平台。然而，考虑到上皮-间质转化（EMT）产生的异质性CTCs，这种方法会遗漏间充质CTCs。值得注意的是，在间充质CTCs上过度表达的N-钙粘蛋白可以促进癌细胞的迁移。因此，我们筛选了一种靶向N-钙粘蛋白的新型肽NP，并通过NP@MNPs开发了一种新的CTCs分离方法，以弥补EpCAM方法的不足。NP@MNPs从加标的人血液中对间充质CTCs具有较高的捕获效率（约85%）。随后，通过NP@MNPs和EP@MNPs在单细胞水平捕获CTCs并进行测序，其RNA谱表明上皮和间充质亚群可以区分。在此，一种新型CTCs分离平台为间充质CTCs分离及后续分子分析奠定了基础。
