Single Cell Polarity in Liquid Phase Facilitates Tumour Metastasis

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Mar 2

PMID 29491397

Citations 23

Authors

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 OConnor

Quentin Muller

Kathleen Schuck

Sebastian Lange

Daniel Hartmann

Saskia Spaich

Olaf Gross

Jochen Utikal

Sebastian Haferkamp

Martin R Sprick

Amruta Damle-Vartak

Alexander Hapfelmeier

Norbert Huser

Ulrike Protzer

Andreas Trumpp

Dieter Saur

Nachiket Vartak

Christoph A Klein

Bernhard Polzer

Lubor Borsig

Mathias Heikenwalder

Affiliations

Soon will be listed here.

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.

Citing Articles

Cellular polarity pilots breast cancer progression and immunosuppression.

Huang J, Luo S, Shen J, Lee M, Chen R, Ma S Oncogene. 2025; .

PMID: 40057606 DOI: 10.1038/s41388-025-03324-0.

Ezrin Polarization as a Diagnostic Marker for Circulating Tumor Cells in Hepatocellular Carcinoma.

Budeyri I, Guckelberger O, Oppermann E, Roy D, Sliwinski S, Becker F Cells. 2025; 14(1.

PMID: 39791707 PMC: 11720075. DOI: 10.3390/cells14010006.

Tumor-treating fields in cancer therapy: advances of cellular and molecular mechanisms.

Xiao T, Zheng H, Zu K, Yue Y, Wang Y Clin Transl Oncol. 2024; 27(1):1-14.

PMID: 38884919 DOI: 10.1007/s12094-024-03551-z.

Cooperative polarization of MCAM/CD146 and ERM family proteins in melanoma.

Miller S, Hoh M, Ebmeier C, Tay J, Ahn N Mol Biol Cell. 2023; 35(3):ar31.

PMID: 38117590 PMC: 10916866. DOI: 10.1091/mbc.E23-06-0255.

Cell polarity changes in cancer initiation and progression.

Peglion F, Etienne-Manneville S J Cell Biol. 2023; 223(1).

PMID: 38091012 PMC: 10720656. DOI: 10.1083/jcb.202308069.

References

Estecha A, Sanchez-Martin L, Puig-Kroger A, Bartolome R, Teixido J, Samaniego R . Moesin orchestrates cortical polarity of melanoma tumour cells to initiate 3D invasion. J Cell Sci. 2009; 122(Pt 19):3492-501. DOI: 10.1242/jcs.053157. View

Polzer B, Medoro G, Pasch S, Fontana F, Zorzino L, Pestka A . Molecular profiling of single circulating tumor cells with diagnostic intention. EMBO Mol Med. 2014; 6(11):1371-86. PMC: 4237466. DOI: 10.15252/emmm.201404033. View

Allen M, Bjerke M, Edlund H, Nelander S, Westermark B . Origin of the U87MG glioma cell line: Good news and bad news. Sci Transl Med. 2016; 8(354):354re3. DOI: 10.1126/scitranslmed.aaf6853. View

Linder S, Wiesner C, Himmel M . Degrading devices: invadosomes in proteolytic cell invasion. Annu Rev Cell Dev Biol. 2011; 27:185-211. DOI: 10.1146/annurev-cellbio-092910-154216. View

Chudziak J, Burt D, Mohan S, Rothwell D, Mesquita B, Antonello J . Clinical evaluation of a novel microfluidic device for epitope-independent enrichment of circulating tumour cells in patients with small cell lung cancer. Analyst. 2015; 141(2):669-78. DOI: 10.1039/c5an02156a. View

Kukulski W, Schorb M, Welsch S, Picco A, Kaksonen M, Briggs J . Correlated fluorescence and 3D electron microscopy with high sensitivity and spatial precision. J Cell Biol. 2011; 192(1):111-9. PMC: 3019550. DOI: 10.1083/jcb.201009037. View

Park J, Kramer B, Lai S, Goldstein L, Gazdar A . Chemosensitivity patterns and expression of human multidrug resistance-associated MDR1 gene by human gastric and colorectal carcinoma cell lines. J Natl Cancer Inst. 1990; 82(3):193-8. DOI: 10.1093/jnci/82.3.193. View

Ponten J, MACINTYRE E . Long term culture of normal and neoplastic human glia. Acta Pathol Microbiol Scand. 1968; 74(4):465-86. DOI: 10.1111/j.1699-0463.1968.tb03502.x. View

Clark E, Golub T, Lander E, Hynes R . Genomic analysis of metastasis reveals an essential role for RhoC. Nature. 2000; 406(6795):532-5. DOI: 10.1038/35020106. View

10.

Ameri K, Luong R, Zhang H, Powell A, Montgomery K, Espinosa I . Circulating tumour cells demonstrate an altered response to hypoxia and an aggressive phenotype. Br J Cancer. 2010; 102(3):561-9. PMC: 2805847. DOI: 10.1038/sj.bjc.6605491. View

11.

Witze E, Litman E, Argast G, Moon R, Ahn N . Wnt5a control of cell polarity and directional movement by polarized redistribution of adhesion receptors. Science. 2008; 320(5874):365-9. PMC: 3229220. DOI: 10.1126/science.1151250. View

12.

Lorentzen A, Bamber J, Sadok A, Elson-Schwab I, Marshall C . An ezrin-rich, rigid uropod-like structure directs movement of amoeboid blebbing cells. J Cell Sci. 2011; 124(Pt 8):1256-67. DOI: 10.1242/jcs.074849. View

13.

Yoshikawa N, Nakamura K, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo M . Suitable indices for evaluating the intensity of tumor metastasis in a mouse experimental metastatic model. In Vivo. 2002; 15(6):485-8. View

14.

Poincloux R, Collin O, Lizarraga F, Romao M, Debray M, Piel M . Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel. Proc Natl Acad Sci U S A. 2011; 108(5):1943-8. PMC: 3033302. DOI: 10.1073/pnas.1010396108. View

15.

Ouhtit A, Gaur R, Abd Elmageed Z, Fernando A, Thouta R, Trappey A . Towards understanding the mode of action of the multifaceted cell adhesion receptor CD146. Biochim Biophys Acta. 2009; 1795(2):130-6. DOI: 10.1016/j.bbcan.2009.01.002. View

16.

Czyz Z, Hoffmann M, Schlimok G, Polzer B, Klein C . Reliable single cell array CGH for clinical samples. PLoS One. 2014; 9(1):e85907. PMC: 3897541. DOI: 10.1371/journal.pone.0085907. View

17.

Dustin M . Hunter to gatherer and back: immunological synapses and kinapses as variations on the theme of amoeboid locomotion. Annu Rev Cell Dev Biol. 2008; 24:577-96. DOI: 10.1146/annurev.cellbio.24.110707.175226. View

18.

Pacifico M, Grover R, Richman P, Daley F, Buffa F, Wilson G . Development of a tissue array for primary melanoma with long-term follow-up: discovering melanoma cell adhesion molecule as an important prognostic marker. Plast Reconstr Surg. 2005; 115(2):367-75. DOI: 10.1097/01.prs.0000148417.86768.c9. View

19.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

20.

Noll E, Eisen C, Stenzinger A, Espinet E, Muckenhuber A, Klein C . CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma. Nat Med. 2016; 22(3):278-87. PMC: 4780258. DOI: 10.1038/nm.4038. View