Abstract
During cancer progression, malignant cells in the tumour invade surrounding tissues. This transformation of adherent cells to a motile phenotype has been associated with the epithelial–mesenchymal transition (EMT). Here, we show that EMT-activated cells migrate through micropillar arrays as a collectively advancing front that scatters individual cells. Individual cells with few neighbours dispersed with fast, straight trajectories, whereas cells that encountered many neighbours migrated collectively with epithelial biomarkers. We modelled these emergent dynamics using a physical analogy to phase transitions during binary-mixture solidification, and validated it using drug perturbations, which revealed that individually migrating cells exhibit diminished chemosensitivity. Our measurements also indicate a degree of phenotypic plasticity as cells interconvert between individual and collective migration. The study of multicellular behaviours with single-cell resolution should enable further quantitative insights into heterogeneous tumour invasion.
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Acknowledgements
We thank J. Taunton for the gift of FMK-MEA, A. Besser and G. Danuser for assistance with cell tracking, and O. Hurtado for assistance with fabrication. This work was supported by the Merck Fellowship of the Damon Runyon Cancer Research Foundation (DRG-2065-10) to I.Y.W., the Howard Hughes Medical Institute to D.A.H., as well as the National Institutes of Health under CA129933 to D.A.H., EB002503 (BioMEMS Resource Center) to M.T., and CA135601 and GM092804 to D.I.
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D.A.H. and D.I. conceived the project; I.Y.W., S.J., D.A.H., M.T. and D.I. designed the research; I.Y.W., S.J. and E.A.W. performed the experiments; I.Y.W. and E.A.W. performed image analysis; I.Y.W., E.A.W. and S.P. performed data analysis; I.Y.W. and M.T. developed the theoretical model; I.Y.W., M.T. and D.I. wrote the manuscript with feedback from S.J., E.A.W., S.P. and D.A.H. All authors reviewed the data and final manuscript.
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Wong, I., Javaid, S., Wong, E. et al. Collective and individual migration following the epithelial–mesenchymal transition. Nature Mater 13, 1063–1071 (2014). https://doi.org/10.1038/nmat4062
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DOI: https://doi.org/10.1038/nmat4062
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