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Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition

2013; American Association for the Advancement of Science; Volume: 339; Issue: 6119 Linguagem: Inglês

10.1126/science.1228522

1095-9203

Min Yu, Aditya Bardia, Ben S. Wittner, Shannon L. Stott, Malgorzata E. Smas, David T. Ting, Steven J. Isakoff, Jordan C. Ciciliano, Marissa Wells, Ajay M. Shah, Kyle Concannon, Maria Donaldson Collier, Lecia V. Sequist, Elena F. Brachtel, Dennis C. Sgroi, José Baselga, Sridhar Ramaswamy, Mehmet Toner, Daniel A. Haber, Shyamala Maheswaran,

FOXO transcription factor regulation

Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in human cancer, we characterized EMT in circulating tumor cells (CTCs) from breast cancer patients. Rare primary tumor cells simultaneously expressed mesenchymal and epithelial markers, but mesenchymal cells were highly enriched in CTCs. Serial CTC monitoring in 11 patients suggested an association of mesenchymal CTCs with disease progression. In an index patient, reversible shifts between these cell fates accompanied each cycle of response to therapy and disease progression. Mesenchymal CTCs occurred as both single cells and multicellular clusters, expressing known EMT regulators, including transforming growth factor (TGF)-β pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer.