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Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction

Jorge Barbazan, Carlos Pérez-González, Manuel Gómez-González, Mathieu Dedenon, Sophie Richon, Ernest Latorre, Marco Serra, Pascale Mariani, Stéphanie Descroix, Pierre Sens, Xavier Trepat, Danijela Matic Vignjevic
doi: https://doi.org/10.1101/2021.04.05.438443
Jorge Barbazan
1Institut Curie, PSL Research University, CNRS UMR 144, F-75005 Paris, France
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Carlos Pérez-González
1Institut Curie, PSL Research University, CNRS UMR 144, F-75005 Paris, France
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Manuel Gómez-González
2Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST), 08028 Barcelona, Spain
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Mathieu Dedenon
3Institut Curie, PSL Research University, CNRS UMR 168, F-75005 Paris, France
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Sophie Richon
1Institut Curie, PSL Research University, CNRS UMR 144, F-75005 Paris, France
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Ernest Latorre
2Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST), 08028 Barcelona, Spain
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Marco Serra
3Institut Curie, PSL Research University, CNRS UMR 168, F-75005 Paris, France
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Pascale Mariani
4Institut Curie, Department of surgical oncology, Curie Institute, F-75005 Paris, France
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Stéphanie Descroix
3Institut Curie, PSL Research University, CNRS UMR 168, F-75005 Paris, France
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Pierre Sens
3Institut Curie, PSL Research University, CNRS UMR 168, F-75005 Paris, France
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Xavier Trepat
2Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST), 08028 Barcelona, Spain
5Facutltat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
6Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
7Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 08028 Barcelona, Spain
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  • For correspondence: danijela.vignjevic@curie.fr xtrepat@ibecbarcelona.eu
Danijela Matic Vignjevic
1Institut Curie, PSL Research University, CNRS UMR 144, F-75005 Paris, France
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  • For correspondence: danijela.vignjevic@curie.fr xtrepat@ibecbarcelona.eu
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Abstract

During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule is a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 05, 2021.
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Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction
Jorge Barbazan, Carlos Pérez-González, Manuel Gómez-González, Mathieu Dedenon, Sophie Richon, Ernest Latorre, Marco Serra, Pascale Mariani, Stéphanie Descroix, Pierre Sens, Xavier Trepat, Danijela Matic Vignjevic
bioRxiv 2021.04.05.438443; doi: https://doi.org/10.1101/2021.04.05.438443
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Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction
Jorge Barbazan, Carlos Pérez-González, Manuel Gómez-González, Mathieu Dedenon, Sophie Richon, Ernest Latorre, Marco Serra, Pascale Mariani, Stéphanie Descroix, Pierre Sens, Xavier Trepat, Danijela Matic Vignjevic
bioRxiv 2021.04.05.438443; doi: https://doi.org/10.1101/2021.04.05.438443

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