RESUMEN
Carcinoma cells undergo epithelial-mesenchymal transition (EMT); however, contributions of EMT heterogeneity to disease progression remain a matter of debate. Here, we addressed the EMT status of ex vivo cultured circulating and disseminated tumor cells (CTCs/DTCs) in a syngeneic mouse model of metastatic breast cancer (MBC). Epithelial-type CTCs with a restricted mesenchymal transition had the strongest lung metastases formation ability, whereas mesenchymal-type CTCs showed limited metastatic ability. EpCAM expression served as a surrogate marker to evaluate the EMT heterogeneity of clinical samples from MBC, including metastases, CTCs, and DTCs. The proportion of epithelial-type CTCs, and especially DTCs, correlated with distant metastases and poorer outcome of patients with MBC. This study fosters our understanding of EMT in metastasis and underpins heterogeneous EMT phenotypes as important parameters for tumor prognosis and treatment. We further suggest that EpCAM-dependent CTC isolation systems will underestimate CTC numbers but will quantify clinically relevant metastatic cells.
Asunto(s)
Neoplasias de la Mama/patología , Células Epiteliales/patología , Transición Epitelial-Mesenquimal/fisiología , Metástasis de la Neoplasia/patología , Animales , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Línea Celular , Molécula de Adhesión Celular Epitelial/metabolismo , Células Epiteliales/metabolismo , Femenino , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , PronósticoRESUMEN
Available online October 16, 2014 This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
