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Cell viscosity influences hematogenous dissemination and metastatic extravasation of tumor cells

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Goswami,  Ruchi
Lab-on-Chip, Core Facilities, Max-Planck-Zentrum für Physik und Medizin, Max Planck Institute for the Science of Light, Max Planck Society;
Guck Division, Max Planck Institute for the Science of Light, Max Planck Society;
Guck Division, Max-Planck-Zentrum für Physik und Medizin, Max Planck Institute for the Science of Light, Max Planck Society;

/persons/resource/persons248004

Girardo,  Salvatore
Guck Division, Max Planck Institute for the Science of Light, Max Planck Society;
Guck Division, Max-Planck-Zentrum für Physik und Medizin, Max Planck Institute for the Science of Light, Max Planck Society;
Lab-on-Chip, Core Facilities, Max-Planck-Zentrum für Physik und Medizin, Max Planck Institute for the Science of Light, Max Planck Society;

/persons/resource/persons248002

Kräter,  Martin
Guck Division, Max Planck Institute for the Science of Light, Max Planck Society;
Guck Division, Max-Planck-Zentrum für Physik und Medizin, Max Planck Institute for the Science of Light, Max Planck Society;

/persons/resource/persons241284

Guck,  Jochen
Guck Division, Max Planck Institute for the Science of Light, Max Planck Society;
Guck Division, Max-Planck-Zentrum für Physik und Medizin, Max Planck Institute for the Science of Light, Max Planck Society;

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Citation

Gensbittel, V., Follain, G., Bochler, L., Uhlmann, K., Lefèbvre, O., Larnicol, A., et al. (2024). Cell viscosity influences hematogenous dissemination and metastatic extravasation of tumor cells. bioRxiv 10.1101/2024.03.28.587171.


Cite as: https://hdl.handle.net/21.11116/0000-0010-7CA4-A
Abstract
Metastases arise from a multi-step process during which tumor cells change their mechanics in response to microenvironmental cues. While such mechanical adaptability could influence metastatic success, how tumor cell mechanics directly impacts intravascular behavior of circulating tumor cells (CTCs) remains poorly understood. In the present study, we demonstrate how the deformability of CTCs affects hematogenous dissemination and identify the mechanical profiles that favor metastatic extravasation. Combining intravital microscopy with CTC-mimicking elastic beads and mechanically-tuned tumor cells, we demonstrate that the inherent properties of circulating objects dictate their ability to enter constraining vessels. We identify cellular viscosity as the key property that governs CTC circulation and arrest patterns. We further demonstrate that cellular viscosity is required for efficient extravasation and find that properties that favor extravasation and subsequent metastatic outgrowth can be opposite. Altogether, we identify CTC viscosity as a key biomechanical parameter that shapes several steps of metastasis.