Single cell polarity in liquid phase facilitates tumour metastasis

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, Knud Esser, Marko Roblek, Felix Kuehne, Gaia Bianco, Tracy O’Connor, Quentin Müller, Kathleen Schuck, Sebastian Lange, Daniel Hartmann, Saskia Spaich, Olaf Groß, Jochen Utikal, Sebastian Haferkamp, Martin R. Sprick, Amruta Damle-Vartak, Alexander Hapfelmeier, Norbert Hüser, Ulrike Protzer, Andreas Trumpp, Dieter Saur, Nachiket Vartak, Christoph A. Klein, Bernhard Polzer, Lubor Borsig and Mathias Heikenwalder ()
Additional contact information
Anna Lorentzen: Technische Universität München, Helmholtz Center Munich (HMGU)
Paul F. Becker: Technische Universität München, Helmholtz Center Munich (HMGU)
Jan Kosla: Technische Universität München, Helmholtz Center Munich (HMGU)
Massimo Saini: Deutsches Krebsforschungszentrum (DKFZ)
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)
Bastian Seubert: Technische Universität München, Helmholtz Center Munich (HMGU)
Marc Ringelhan: Technische Universität München, Helmholtz Center Munich (HMGU)
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)
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)
Sebastian Haferkamp: University Hospital Regensburg
Martin R. Sprick: Deutsches Krebsforschungszentrum (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)
Dieter Saur: Klinikum rechts der Isar, Technische Universität München
Nachiket Vartak: Leibnitz Research Cenrtre for Working Environment and Human Factors (IfADo)
Christoph A. Klein: Fraunhofer-Institut für Toxikologie und Experimentelle Medizin
Bernhard Polzer: Fraunhofer-Institut für Toxikologie und Experimentelle Medizin
Lubor Borsig: University of Zurich
Mathias Heikenwalder: Technische Universität München, Helmholtz Center Munich (HMGU)

Nature Communications, 2018, vol. 9, issue 1, 1-20

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03139-6

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