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 LangeDaniel 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, Mathias Heikenwalder

*Corresponding author af dette arbejde

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    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.

    OriginalsprogEngelsk
    Artikelnummer887
    TidsskriftNature Communications
    Vol/bind9
    Nummer1
    Antal sider20
    ISSN2041-1723
    DOI
    StatusUdgivet - 1 dec. 2018

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