Oleksandr Chepizhkoa, Josep-Maria Armengol-Colladob, Stephanie Alexander, Esther Wagenae, Bettina Weigelin, Luca Giomi, Peter Friedl, Stefano Zapperi,Caterina A. M. La Porta
DOI: https://doi.org/10.1073/pnas.2414009121
Abstract: Cancer metastasis involves the collective migration of cancer cells in confined space, a problem that has been widely investigated in vitro. Here, we quantify the flow patterns of cancer cell as they invade tissue space and deform the surrounding extracellular matrix in vivo. Cell motion self-organizes into well-defined traffic lanes aligned along interstitial tracks and resembles the flow of a turbulent active fluid. Our study provides insights into the mechanisms underlying tumor invasion and sheds light on physical factors contributing to metastatic spread.
Collective migration of cancer cells is often interpreted using concepts derived from the physics of active matter, but the experimental evidence is mostly restricted to observations made in vitro. Here, we study collective invasion of metastatic cancer cells injected into the mouse deep dermis using intravital multiphoton microscopy combined with a skin window technique and three-dimensional quantitative image analysis. We observe a multicellular but low-cohesive migration mode characterized by rotational patterns which self-organize into antiparallel persistent tracks with orientational nematic order. We analyze the deformations induced by the cells in the extracellular matrix and find broadly distributed strain bands with a prevalence of compression. A model of active nematic hydrodynamics is able to describe several statistical features of the experimentally observed flow, suggesting that collective cancer cell invasion can be interpreted as a nematic active fluid in the turbulent regime. Our results help elucidate the migration patterns of cancer cells in vivo and provide quantitative guidance for the development of realistic in vitro and in silico models for collective cell migration.
DOI: None
Zenodo URL: None
Created at: 15th May 2025 at 19:07
Intravital Microscopy
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P.FRI-250515-V1_IntravitalMircoscopyofTumorCellInvasion.docx
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- IntravitalMircoscopyofTumorCellInvasion.docx
Imaging Analysis - Data Linked
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P.FRI-250515-V1_IntravitalMircoscopyofTumorCellInvasion.docx
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- IntravitalMircoscopyofTumorCellInvasion.docx
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Created: 15th May 2025 at 19:07