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Nat Commun. 2018 Feb 28;9(1):887. doi: 10.1038/s41467-018-03139-6.

Single cell polarity in liquid phase facilitates tumour metastasis.

Author information

1
Institute of Virology, Technische Universität München, Helmholtz Center Munich (HMGU), 81675, Munich, Germany. anna@mbg.au.dk.
2
Department of Molecular Biology and Genetics, Aarhus University, 8000, Aarhus, Denmark. anna@mbg.au.dk.
3
Institute of Virology, Technische Universität München, Helmholtz Center Munich (HMGU), 81675, Munich, Germany.
4
Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, 14220, Prague, Czech Republic.
5
Divison of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
6
Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120, Heidelberg, Germany.
7
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH, 69120, Heidelberg, Germany.
8
Project Group Personalized Tumour Therapy, Fraunhofer-Institut für Toxikologie und Experimentelle Medizin, 93053, Regensburg, Germany.
9
Electron Microscopy Core Facility, European Molecular Biology Laboratory (EMBL), 69117, Heidelberg, Germany.
10
Department of Surgical Pathology, University Hospital Zurich, 8091, Zurich, Switzerland.
11
Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675, Munich, Germany.
12
Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, 8057, Zurich, Switzerland.
13
Department of Surgery, Klinikum rechts der Isar, Technische Universität München, 81675, Munich, Germany.
14
Frauenklinik, University Medical Centre Mannheim, 68167, Mannheim, Germany.
15
Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, 81675, Munich, Germany.
16
Skin Cancer Unit, Deutsches Krebsforschungszentrum (DKFZ), 69120, Heidelberg, Germany.
17
Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167, Mannheim, Germany.
18
Department of Dermatology, University Hospital Regensburg, 93042, Regensburg, Germany.
19
German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
20
Department of Systems Toxicology, Leibnitz Research Cenrtre for Working Environment and Human Factors (IfADo), 44139, Dortmund, Germany.
21
Institut für Medizinische Statistik und Epidemiologie, Klinikum rechts der Isar, Technische Universität München, 81675, Munich, Germany.
22
Chair of Experimental Medicine and Therapy Research, University of Regensburg, 93053, Regensburg, Germany.
23
Institute of Virology, Technische Universität München, Helmholtz Center Munich (HMGU), 81675, Munich, Germany. m.heikenwaelder@dkfz.de.
24
Divison of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. m.heikenwaelder@dkfz.de.

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.

PMID:
29491397
PMCID:
PMC5830403
DOI:
10.1038/s41467-018-03139-6
[Indexed for MEDLINE]
Free PMC Article

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