EMT and EGFR in CTCs cytokeratin negative non-metastatic breast cancer

CTC 细胞角蛋白阴性非转移性乳腺癌中的 EMT 和 EGFR

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作者:Maria J Serrano, Francisco G Ortega, Maria J Alvarez-Cubero, Rosa Nadal, Pedro Sanchez-Rovira, Marta Salido, María Rodríguez, Jose L García-Puche, Miguel Delgado-Rodriguez, Francisco Solé, Maria A García, Macarena Perán, Rafael Rosell, Juan A Marchal, Jose A Lorente

Abstract

Circulating tumor cells (CTCs) are frequently associated with epithelial-mesenchymal transition (EMT).The objective of this study was to detect EMT phenotype through Vimentin (VIM) and Slug expression in cytokeratin (CK)-negative CTCs in non-metastatic breast cancer patients and to determine the importance of EGFR in the EMT phenomenon. In CK-negative CTCs samples, both VIM and Slug markers were co-expressed in the most of patients. Among patients EGFR+, half of them were positive for these EMT markers. Furthermore, after a systemic treatment 68% of patients switched from CK- to CK+ CTCs. In our experimental model we found that activation of EGFR signaling by its ligand on MCF-7 cells is sufficient to increase EMT phenotypes, to inhibit apoptotic events and to induce the loss of CK expression. The simultaneous detection of both EGFR and EMT markers in CTCs may improve prognostic or predictive information in patients with operable breast cancer.

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