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Single cell polarity in liquid phase facilitates tumour metastasis

Author

Listed:
  • Anna Lorentzen

    (Technische Universität München, Helmholtz Center Munich (HMGU)
    Aarhus University)

  • Paul F. Becker

    (Technische Universität München, Helmholtz Center Munich (HMGU))

  • Jan Kosla

    (Technische Universität München, Helmholtz Center Munich (HMGU)
    Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic
    German Cancer Research Center (DKFZ))

  • Massimo Saini

    (Deutsches Krebsforschungszentrum (DKFZ)
    Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH)

  • Kathrin Weidele

    (Fraunhofer-Institut für Toxikologie und Experimentelle Medizin)

  • Paolo Ronchi

    (European Molecular Biology Laboratory (EMBL))

  • Corinna Klein

    (Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH)

  • Monika J. Wolf

    (University Hospital Zurich)

  • Felix Geist

    (Deutsches Krebsforschungszentrum (DKFZ)
    Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH)

  • Bastian Seubert

    (Technische Universität München, Helmholtz Center Munich (HMGU)
    German Cancer Research Center (DKFZ))

  • Marc Ringelhan

    (Technische Universität München, Helmholtz Center Munich (HMGU)
    Klinikum rechts der Isar, Technische Universität München)

  • Daniela Mihic-Probst

    (University Hospital Zurich)

  • Knud Esser

    (Technische Universität München, Helmholtz Center Munich (HMGU))

  • Marko Roblek

    (University of Zurich)

  • Felix Kuehne

    (Technische Universität München, Helmholtz Center Munich (HMGU))

  • Gaia Bianco

    (Technische Universität München, Helmholtz Center Munich (HMGU))

  • Tracy O’Connor

    (Technische Universität München, Helmholtz Center Munich (HMGU)
    German Cancer Research Center (DKFZ))

  • Quentin Müller

    (Klinikum rechts der Isar, Technische Universität München)

  • Kathleen Schuck

    (Klinikum rechts der Isar, Technische Universität München)

  • Sebastian Lange

    (Klinikum rechts der Isar, Technische Universität München)

  • Daniel Hartmann

    (Klinikum rechts der Isar, Technische Universität München)

  • Saskia Spaich

    (University Medical Centre Mannheim)

  • Olaf Groß

    (Klinikum rechts der Isar, Technische Universität München)

  • Jochen Utikal

    (Deutsches Krebsforschungszentrum (DKFZ)
    University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg)

  • Sebastian Haferkamp

    (University Hospital Regensburg)

  • Martin R. Sprick

    (Deutsches Krebsforschungszentrum (DKFZ)
    Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH
    German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ))

  • Amruta Damle-Vartak

    (Leibnitz Research Cenrtre for Working Environment and Human Factors (IfADo))

  • Alexander Hapfelmeier

    (Klinikum rechts der Isar, Technische Universität München)

  • Norbert Hüser

    (Klinikum rechts der Isar, Technische Universität München)

  • Ulrike Protzer

    (Technische Universität München, Helmholtz Center Munich (HMGU))

  • Andreas Trumpp

    (Deutsches Krebsforschungszentrum (DKFZ)
    Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH
    German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ))

  • Dieter Saur

    (Klinikum rechts der Isar, Technische Universität München
    German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ))

  • Nachiket Vartak

    (Leibnitz Research Cenrtre for Working Environment and Human Factors (IfADo))

  • Christoph A. Klein

    (Fraunhofer-Institut für Toxikologie und Experimentelle Medizin
    University of Regensburg)

  • Bernhard Polzer

    (Fraunhofer-Institut für Toxikologie und Experimentelle Medizin)

  • Lubor Borsig

    (University of Zurich)

  • Mathias Heikenwalder

    (Technische Universität München, Helmholtz Center Munich (HMGU)
    German Cancer Research Center (DKFZ))

Abstract

Dynamic polarisation of tumour cells is essential for metastasis. While the role of polarisation during dedifferentiation and migration is well established, polarisation of metastasising tumour cells during phases of detachment has not been investigated. Here we identify and characterise a type of polarisation maintained by single cells in liquid phase termed single-cell (sc) polarity and investigate its role during metastasis. We demonstrate that sc polarity is an inherent feature of cells from different tumour entities that is observed in circulating tumour cells in patients. Functionally, we propose that the sc pole is directly involved in early attachment, thereby affecting adhesion, transmigration and metastasis. In vivo, the metastatic capacity of cell lines correlates with the extent of sc polarisation. By manipulating sc polarity regulators and by generic depolarisation, we show that sc polarity prior to migration affects transmigration and metastasis in vitro and in vivo.

Suggested Citation

  • Anna Lorentzen & Paul F. Becker & Jan Kosla & Massimo Saini & Kathrin Weidele & Paolo Ronchi & Corinna Klein & Monika J. Wolf & Felix Geist & Bastian Seubert & Marc Ringelhan & Daniela Mihic-Probst & , 2018. "Single cell polarity in liquid phase facilitates tumour metastasis," Nature Communications, Nature, vol. 9(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03139-6
    DOI: 10.1038/s41467-018-03139-6
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