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Single cell polarity in liquid phase facilitates tumour metastasis

: Lorentzen, Anna; Becker, Paul F.; Kosla, Jan; Saini, Massimo; Weidele, Kathrin; Ronchi, Paolo; Klein, Corinna; Wolf, Monika J.; Geist, Felix; Seubert, Bastian; Ringelhan, Marc; Mihic-Probst, Daniela; Esser, Knud; Roblek, Marko; Kuehne, Felix; Bianco, Gaia; O'Connor, Tracy; Müller, Quentin; Schuck, Kathleen; Lange, Sebastian; Hartmann, Daniel; Spaich, Saskia; Gross, Olaf; Utikal, Jochen; Haferkamp, Sebastian; Sprick, Martin R.; Damle-Vartak, Amruta; Hapfelmeier, Alexander; Hüser, Norbert; Protzer, Ulrike; Trumpp, Andreas; Saur, Dieter; Vartak, Nachiket; Klein, Christoph A.; Polzer, Bernhard; Borsig, Lubor; Heikenwalder, Mathias

Fulltext urn:nbn:de:0011-n-4972372 (6.1 MByte PDF)
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Created on: 22.6.2018

Nature Communications 9 (2018), Art. 887, 20 pp.
ISSN: 2041-1723
Journal Article, Electronic Publication
Fraunhofer ITEM ()
cell line, tumor; cell movement; Mice, Inbred C57BL; metastasis; neoplasm; neoplastic cell

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.