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Epithelial-type systemic breast carcinoma cells with a restricted mesenchymal transition are a major source of metastasis.
Liu, Xiao; Li, Junjian; Cadilha, Bruno Loureiro; Markota, Anamarija; Voigt, Cornelia; Huang, Zhe; Lin, Peter P; Wang, Daisy D; Dai, Juncheng; Kranz, Gisela; Krandick, Anna; Libl, Darko; Zitzelsberger, Horst; Zagorski, Isabella; Braselmann, Herbert; Pan, Min; Zhu, Sibo; Huang, Yuanchi; Niedermeyer, Sebastian; Reichel, Christoph A; Uhl, Bernd; Briukhovetska, Daria; Suárez, Javier; Kobold, Sebastian; Gires, Olivier; Wang, Hongxia.
Afiliación
  • Liu X; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany.
  • Li J; Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
  • Cadilha BL; Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, Department of Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Lindwurmstrasse 2a, 80337 Munich, Germany.
  • Markota A; Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, Department of Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Lindwurmstrasse 2a, 80337 Munich, Germany.
  • Voigt C; Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, Department of Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Lindwurmstrasse 2a, 80337 Munich, Germany.
  • Huang Z; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany.
  • Lin PP; Cytelligen, San Diego, CA 92121, USA.
  • Wang DD; Cytelligen, San Diego, CA 92121, USA.
  • Dai J; Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
  • Kranz G; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany.
  • Krandick A; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany.
  • Libl D; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany.
  • Zitzelsberger H; Clinical Cooperation Group Personalized Radiotherapy of Head and Neck Tumors, Helmholtz Zentrum München, Neuherberg, Germany.
  • Zagorski I; Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Neuherberg, Germany.
  • Braselmann H; Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
  • Pan M; Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Neuherberg, Germany.
  • Zhu S; Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Neuherberg, Germany.
  • Huang Y; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany.
  • Niedermeyer S; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.
  • Reichel CA; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany.
  • Uhl B; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany.
  • Briukhovetska D; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany.
  • Suárez J; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany.
  • Kobold S; Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, Department of Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Lindwurmstrasse 2a, 80337 Munich, Germany.
  • Gires O; Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, Department of Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Lindwurmstrasse 2a, 80337 Munich, Germany.
  • Wang H; Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, Department of Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Lindwurmstrasse 2a, 80337 Munich, Germany.
Sci Adv ; 5(6): eaav4275, 2019 06.
Article en En | MEDLINE | ID: mdl-31223646
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)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Células Epiteliales / Transición Epitelial-Mesenquimal / Metástasis de la Neoplasia Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Adv Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Células Epiteliales / Transición Epitelial-Mesenquimal / Metástasis de la Neoplasia Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Adv Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos