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循环肿瘤细胞 EMT 的动态监测作为癌症转移的指标。

Dynamic Monitoring of EMT in CTCs as an Indicator of Cancer Metastasis.

机构信息

Centre for Personalized Nanomedicine, Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.

Dermatology Research Centre, University of Queensland Diamantina Institute, University of Queensland, Brisbane, QLD 4102, Australia.

出版信息

Anal Chem. 2021 Dec 21;93(50):16787-16795. doi: 10.1021/acs.analchem.1c03167. Epub 2021 Dec 10.

DOI:10.1021/acs.analchem.1c03167
PMID:34889595
Abstract

Epithelial to mesenchymal transition (EMT) results in the genesis of circulating tumor cells (CTCs) from tumor sites and promotes the metastatic capability of CTCs in circulation. In this study, we develop a multiplex surface-enhanced Raman scattering nanotechnology for comprehensive characterization of EMT-associated phenotypes in CTCs, to monitor cancer metastasis. We observe the downregulation of the CTC marker (EpCAM) and the epithelial marker (E-cadherin), as well as the upregulation of a mesenchymal marker (N-cadherin) and a stem cell marker (ABCB5) during the transforming growth factor-β-induced EMT process in breast cancer cell line models. Additionally, we also find changes in the heterogeneity levels of these selected markers in cells. With this method, we successfully detect the presence of disease in samples from breast cancer patients and characterize EMT-associated phenotypes in their CTCs. Overall, this approach and findings provide a new means for monitoring the EMT process in cancer, insights into the detailed mechanistic progress of the diseases, and have potential for detecting the early occurrence of cancer metastasis.

摘要

上皮-间充质转化(EMT)导致肿瘤部位的循环肿瘤细胞(CTC)的产生,并促进CTC 在循环中的转移能力。在这项研究中,我们开发了一种多重表面增强拉曼散射纳米技术,用于全面表征 CTC 中的 EMT 相关表型,以监测癌症转移。我们观察到在转化生长因子-β诱导的乳腺癌细胞系模型中的 EMT 过程中,CTC 标志物(EpCAM)和上皮标志物(E-钙黏蛋白)下调,以及间充质标志物(N-钙黏蛋白)和干细胞标志物(ABCB5)上调。此外,我们还发现这些选定标志物在细胞中的异质性水平发生变化。通过这种方法,我们成功地在来自乳腺癌患者的样本中检测到疾病的存在,并在其 CTC 中表征 EMT 相关表型。总的来说,这种方法和发现为监测癌症中的 EMT 过程提供了一种新的手段,深入了解疾病的详细机制进展,并有可能检测到癌症转移的早期发生。

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