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TROP2在三阴性乳腺癌循环肿瘤细胞(CTCs)中高表达,是上皮间质转化CTCs的潜在标志物。

TROP2 is highly expressed in triple-negative breast cancer CTCs and is a potential marker for epithelial mesenchymal CTCs.

作者信息

Liao Qingyu, Zhang Ruiming, Ou Zuli, Ye Yan, Zeng Qian, Wang Yange, Wang Anqi, Chen Tingmei, Chai Chengsen, Guo Bianqin

机构信息

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing100190, China.

出版信息

Mol Ther Oncol. 2024 Jan 10;32(1):200762. doi: 10.1016/j.omton.2024.200762. eCollection 2024 Mar 21.

Abstract

Circulating tumor cells (CTCs) are the seeds of distant metastases of malignant tumors and are associated with malignancy and risk of metastasis. However, tumor cells undergo epithelial-mesenchymal transition (EMT) during metastasis, leading to the emergence of different types of CTCs. Real-time dynamic molecular and functional typing of CTCs is necessary to precisely guide personalized treatment. Most CTC detection systems are based on epithelial markers that may fail to detect EMT CTCs. Therefore, it is clinically important to identify new markers of different CTC types. In this study, bioinformatics analysis and experimental assays showed that trophoblast cell surface antigen 2 (TROP2), a target molecule for advanced palliative treatment of triple-negative breast cancer (TNBC), was highly expressed in TNBC tissues and tumor cells. Furthermore, TROP2 can promote the migration and invasion of TNBC cells by upregulating EMT markers. The specificity and potential of TROP2 as an EMT-associated marker of TNBC CTCs were evaluated by flow cytometry, immunofluorescence, spiking experiments, and a well-established CTC assay. The results indicated that TROP2 is a potential novel CTC marker associated with EMT, providing a basis for more efficacious markers that encompass CTC heterogeneity in patients with TNBC.

摘要

循环肿瘤细胞(CTCs)是恶性肿瘤远处转移的种子,与肿瘤的恶性程度和转移风险相关。然而,肿瘤细胞在转移过程中会经历上皮-间质转化(EMT),导致不同类型CTCs的出现。对CTCs进行实时动态分子和功能分型对于精确指导个性化治疗至关重要。大多数CTCs检测系统基于上皮标志物,可能无法检测到经历EMT的CTCs。因此,识别不同CTCs类型的新标志物具有重要临床意义。在本研究中,生物信息学分析和实验检测表明,滋养层细胞表面抗原2(TROP2)作为三阴性乳腺癌(TNBC)晚期姑息治疗的靶分子,在TNBC组织和肿瘤细胞中高表达。此外,TROP2可通过上调EMT标志物促进TNBC细胞的迁移和侵袭。通过流式细胞术、免疫荧光、加标实验和成熟的CTCs检测方法评估了TROP2作为TNBC CTCs中与EMT相关标志物的特异性和潜力。结果表明,TROP2是一种与EMT相关的潜在新型CTCs标志物,为涵盖TNBC患者CTCs异质性的更有效标志物提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35db/10869581/a030847828bb/fx1.jpg

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