Journal
SCIENCE
Volume 339, Issue 6119, Pages 580-584Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1228522
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Funding
- Breast Cancer Research Foundation
- Stand Up To Cancer
- Susan G. Komen for the Cure [KG090412]
- NIBIB [EB008047]
- NCI [CA129933]
- National Cancer Institute-MGH Federal Share Program
- Howard Hughes Medical Institute
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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)-beta pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer.
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