A1 Refereed original research article in a scientific journal
Cell viscosity influences haematogenous dissemination and metastatic extravasation of tumour cells
Authors: Gensbittel, Valentin; Yesilata, Zeynep; Bochler, Louis; Follain, Gautier; Nemoz-Billet, Laurie; Lefebvre, Olivier; Uhlmann, Klemens; Larnicol, Annabel; Ammirati, Giulia E. M.; Harlepp, Sébastien; Goswami, Ruchi; Girardo, Salvatore; Paulen, Laetitia; Hyenne, Vincent; Mittelheisser, Vincent; Stemmelen, Tristan; Molitor, Anne; Carapito, Raphael; Belthier, Guillaume; Pannequin, Julie; Kräter, Martin; Müller, Daniel J.; Balzani, Daniel; Guck, Jochen; Osmani, Naël; Goetz, Jacky G.
Publisher: Springer Science and Business Media LLC
Publication year: 2026
Journal: Nature Materials
ISSN: 1476-1122
eISSN: 1476-4660
DOI: https://doi.org/10.1038/s41563-025-02462-w
Publication's open availability at the time of reporting: No Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://doi.org/10.1038/s41563-025-02462-w
Metastases arise from a multistep process during which tumour cells face several microenvironmental mechanical challenges, which influence metastatic success. However, how circulating tumour cells (CTCs) adapt their mechanics to such microenvironments is not fully understood. Here we report that the deformability of CTCs affects their haematogenous dissemination and identify mechanical phenotypes that favour metastatic extravasation. Combining intravital microscopy with CTC-mimicking elastic beads, mechanical tuning in tumour lines and profiling of tumour-patient-derived cells, we demonstrate that the inherent mechanical properties of circulating objects dictate their ability to enter constraining vessels. We identify cellular viscosity as a rheostat of CTC circulation and arrest, and show that cellular viscosity is crucial for efficient extravasation. Moreover, we find that mechanical properties that favour extravasation and subsequent metastatic outgrowth can be opposite. Altogether, our results establish CTC viscosity as a key biomechanical parameter that shapes several steps of metastasis.
Funding information in the publication:
We thank all members of J.G.G.’s team for their constant helpful discussions throughout this investigation. J.G.G. is the coordinator of the NANOTUMOR Consortium, a program from ITMO Cancer of Alliance Nationale pour les Sciences de la Vie et de la Santé (AVIESAN), National Alliance for Life Sciences and Health within the framework of the Cancer Plan (France). Work and people in J.G.G.’s laboratory are mostly supported by the Institut National Du Cancer (INCa), French National Cancer Institute, charities (La Ligue contre le Cancer, Association pour la Recherche contre le Cancer (ARC) and Fondation pour la Recherche Médicale (FRM)), the National Plan Cancer Initiative, the Region Grand Est, INSERM and the University of Strasbourg, as well as from local donors (Rohan Athlétisme Saverne, Trailers De La Rose and Club Féminin Lampertheim). This work has been directly funded by support from the Ligue Contre le Cancer (labelisation) and the association Ruban Rose, with additional support from INCa. V.G. has been funded by INSERM, region Grand Est and La Ligue Contre le Cancer. La Ligue Contre le Cancer provided support to Z.Y. and G.F. L.B. and L.N.-B. are supported by FRM (ECO202206015567). K.U. is funded by the Deutsche Forschungsgemeinschaft (DFG), project ID 467937258. V.M. was funded by a PhD fellowship from the French Ministry of Science (MESRI) and by the Foundation ARC. J.G. acknowledges core funding by the Max Planck Society. D.J.M. acknowledges funding by the Swiss National Science Foundation (grant number 310030_215690/1). The production and characterization of the polyacrylamide beads used in this study were supported by the European Union Horizon 2020 research and innovation programme number 953121 (project FLAMIN-GO). R.G. is supported by the FLAMIN-GO project. We thank P. Kessler and I. Busnelli from PICSTRA (CRBS). We thank the animal facility PEFRE (CRBS). We thank P. Patel, part of the TDSU Lab-on-a-chip systems at MPL, for the production of the master template and microfluidic chips used for the bead production. We thank U. Appelt and M. Mroz of the Core Unit Cell Sorting and Immunomonitoring of the Nikolaus Fiebiger Centre for Molecular Medicine (NFZ) at the Friedrich-Alexander University Erlangen-Nuremberg for their technical support in bead sorting. We thank R. Lo, S. Tarte-Deckert and M. Deckert for providing the M229 R/S cell lines. We thank A. Detappe for providing access to the MPA setup. We thank J. Vitre for their help with culturing the CTC-45 and CPP-45 patient-derived cell lines. This work is dedicated to the memory of our co-author Jochen Guck in gratitude for his friendship and scientific vision.
