Epithelial-type systemic breast carcinoma cells with a restricted mesenchymal transition are a major source of metastasis
| Autor: | Olivier Gires, Hongxia Wang, Xiao Liu, Bernd Uhl, Darko Libl, Daisy D. Wang, H. Braselmann, Yuanchi Huang, Juncheng Dai, Cornelia Voigt, Junjian Li, Javier Suárez, Bruno L. Cadilha, Min Pan, Isabella Zagorski, Anna Krandick, Christoph A. Reichel, Sebastian Niedermeyer, Sebastian Kobold, Sibo Zhu, Daria Briukhovetska, Peter Lin, Gisela Kranz, Zhe Huang, Horst Zitzelsberger, Anamarija Markota |
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| Rok vydání: | 2019 |
| Předmět: |
Epithelial-Mesenchymal Transition
Lung Neoplasms Breast Neoplasms Metastasis Cell Line 03 medical and health sciences Mice 0302 clinical medicine medicine Carcinoma Biomarkers Tumor Animals Neoplasm Metastasis skin and connective tissue diseases Research Articles 030304 developmental biology Cancer 0303 health sciences Multidisciplinary Lung business.industry Surrogate endpoint Mesenchymal stem cell digestive oral and skin physiology SciAdv r-articles Epithelial Cells medicine.disease Epithelial Cell Adhesion Molecule Prognosis Metastatic breast cancer 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Female Breast carcinoma business Ex vivo Research Article |
| Zdroj: | Science Advances Sci. Adv. 5:eaav4275 (2019) |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.aav4275 |
| Popis: | Association of epithelial-mesenchymal transition with the metastatic potential of disseminated cells in breast cancer was studied. 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. |
| Databáze: | OpenAIRE |
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