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

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

doi:10.1016/j.omton.2024.200762

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

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

Authors

Qingyu Liao¹, Ruiming Zhang¹, Zuli Ou¹, Yan Ye¹, Qian Zeng¹, Yange Wang¹, Anqi Wang², Tingmei Chen¹, Chengsen Chai¹, Bianqin Guo^{1

3}

Affiliations

¹ Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
² 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.
³ Department of Clinical Laboratory, Chongqing University Cancer Hospital, Chongqing 40030, China.

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.

Keywords: CTCs; EMT; MT: Regular Issue; TNBC; TROP2; biomarker; circulating tumor cells; epithelial-mesenchymal transition; triple-negative breast cancer; trophoblast cell surface antigen 2.