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Liu, X.* ; Li, J.* ; Cadilha, B.L.* ; Markota, A.* ; Voigt, C.* ; Huang, Z.* ; Lin, P.P.* ; Wang, D.D.* ; Dai, J.* ; Kranz, G.* ; Krandick, A.* ; Libl, D.* ; Zitzelsberger, H. ; Zagorski, I. ; Braselmann, H. ; Pan, M.* ; Zhu, S.* ; Huang, Y.* ; Niedermeyer, S.* ; Reichel, C.A.* ; Uhl, B.* ; Briukhovetska, D.* ; Suárez, J.* ; Kobold, S.* ; Gires, O. ; Wang, H.*

Epithelial-type systemic breast carcinoma cells with a restricted mesenchymal transition are a major source of metastasis.

Sci. Adv. 5:eaav4275 (2019)
Publ. Version/Full Text Postprint Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Circulating Tumor-cells; Cancer-patients; Emt; Dissemination; Challenges; Survival
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Quellenangaben Volume: 5, Issue: 6, Pages: , Article Number: eaav4275 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Reviewing status Peer reviewed
Institute(s) CCG Personalized Radiotherapy in Head and Neck Cancer (KKG-KRT)
Research Unit Radiation Cytogenetics (ZYTO)