Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration

Cancer cell extravasation, a key step in the metastatic cascade, involves cancer cell arrest on the endothelium, transendothelial migration (TEM), followed by the invasion into the subendothelial extracellular matrix (ECM) of distant tissues. While cancer research has mostly focused on the biomechan...

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Autores: Javanmardi, Yousef, Agrawal, Ayushi, Malandrino, Andrea, Lasli, Soufian, Chen, Michelle, Shahreza, Somayeh, Serwinski, Bianca, Cammoun, Leila, Li, Ran, Jorfi, Mehdi, Djordjevic, Boris, Szita, Nicolás, Spill, Fabián, Bertazzo, Sergio, Sheridan, Graham K., Shenoy, Vivek, Calvo, Fernando, Kamm, Roger, Moeendarbary, Emad
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/348528
Acceso en línea:http://hdl.handle.net/10261/348528
https://api.elsevier.com/content/abstract/scopus_id/85152548921
Access Level:acceso abierto
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spelling Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial MigrationJavanmardi, YousefAgrawal, AyushiMalandrino, AndreaLasli, SoufianChen, MichelleShahreza, SomayehSerwinski, BiancaCammoun, LeilaLi, RanJorfi, MehdiDjordjevic, BorisSzita, NicolásSpill, FabiánBertazzo, SergioSheridan, Graham K.Shenoy, VivekCalvo, FernandoKamm, RogerMoeendarbary, EmadCancer cell extravasation, a key step in the metastatic cascade, involves cancer cell arrest on the endothelium, transendothelial migration (TEM), followed by the invasion into the subendothelial extracellular matrix (ECM) of distant tissues. While cancer research has mostly focused on the biomechanical interactions between tumor cells (TCs) and ECM, particularly at the primary tumor site, very little is known about the mechanical properties of endothelial cells and the subendothelial ECM and how they contribute to the extravasation process. Here, an integrated experimental and theoretical framework is developed to investigate the mechanical crosstalk between TCs, endothelium and subendothelial ECM during in vitro cancer cell extravasation. It is found that cancer cell actin-rich protrusions generate complex push-pull forces to initiate and drive TEM, while transmigration success also relies on the forces generated by the endothelium. Consequently, mechanical properties of the subendothelial ECM and endothelial actomyosin contractility that mediate the endothelial forces also impact the endothelium's resistance to cancer cell transmigration. These results indicate that mechanical features of distant tissues, including force interactions between the endothelium and the subendothelial ECM, are key determinants of metastatic organotropism.E.M. is grateful for Welcome Trust-MIT Fellowship (WT103883). Y.J. and E.M. acknowledge financial support by Leverhulme Trust Research Project Grant (RPG-2018-443) and the Cancer Research UK Multidisciplinary Award (C57744/A22057). Y.J., E.M., and F.S are grateful for Biotechnology and Biological Sciences Research Council Grant (BB/V001418/1) supports. R.K. and V.S. acknowledge the support from NIH (U54CA261694). F.S. was supported by a UKRI Future Leaders Fellowship, grant number [MR/T043571/1]. F.C. was funded by MCIN/AEI/ 10.13039/501100011033 (RYC-2016-20352, RTI2018-096778-A-I00, PID2021-128107OB-I00); AECC (LABAE19044CALV, PRYCO211372RODR); BBVA Leonardo Awards (IN[19]_BBM_BAS_0076), Cancer Research UK (C57744/A22057) and the ERC (Consolidator Grant 101045756).Peer reviewedJohn Wiley & SonsWellcome TrustLeverhulme TrustCancer Research UKBiotechnology and Biological Sciences Research Council (UK)National Institutes of Health (US)Ministerio de Ciencia, Innovación y Universidades (España)Ministerio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)Asociación Española Contra el CáncerBBVACancer Research UKEuropean Research CouncilConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/348528https://api.elsevier.com/content/abstract/scopus_id/85152548921reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI//RYC-2016-20352,info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-096778-A-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-128107OB-I00Advanced science (Weinheim, Baden-Wurttemberg, Germany)The underlying dataset has been published as supplementary material of the article in the publisher platform at 10.1002/advs.202206554https://doi.org/10.1002/advs.202206554Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3485282026-05-22T06:33:51Z
dc.title.none.fl_str_mv Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration
title Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration
spellingShingle Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration
Javanmardi, Yousef
title_short Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration
title_full Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration
title_fullStr Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration
title_full_unstemmed Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration
title_sort Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration
dc.creator.none.fl_str_mv Javanmardi, Yousef
Agrawal, Ayushi
Malandrino, Andrea
Lasli, Soufian
Chen, Michelle
Shahreza, Somayeh
Serwinski, Bianca
Cammoun, Leila
Li, Ran
Jorfi, Mehdi
Djordjevic, Boris
Szita, Nicolás
Spill, Fabián
Bertazzo, Sergio
Sheridan, Graham K.
Shenoy, Vivek
Calvo, Fernando
Kamm, Roger
Moeendarbary, Emad
author Javanmardi, Yousef
author_facet Javanmardi, Yousef
Agrawal, Ayushi
Malandrino, Andrea
Lasli, Soufian
Chen, Michelle
Shahreza, Somayeh
Serwinski, Bianca
Cammoun, Leila
Li, Ran
Jorfi, Mehdi
Djordjevic, Boris
Szita, Nicolás
Spill, Fabián
Bertazzo, Sergio
Sheridan, Graham K.
Shenoy, Vivek
Calvo, Fernando
Kamm, Roger
Moeendarbary, Emad
author_role author
author2 Agrawal, Ayushi
Malandrino, Andrea
Lasli, Soufian
Chen, Michelle
Shahreza, Somayeh
Serwinski, Bianca
Cammoun, Leila
Li, Ran
Jorfi, Mehdi
Djordjevic, Boris
Szita, Nicolás
Spill, Fabián
Bertazzo, Sergio
Sheridan, Graham K.
Shenoy, Vivek
Calvo, Fernando
Kamm, Roger
Moeendarbary, Emad
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Wellcome Trust
Leverhulme Trust
Cancer Research UK
Biotechnology and Biological Sciences Research Council (UK)
National Institutes of Health (US)
Ministerio de Ciencia, Innovación y Universidades (España)
Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
Asociación Española Contra el Cáncer
BBVA
Cancer Research UK
European Research Council
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Cancer cell extravasation, a key step in the metastatic cascade, involves cancer cell arrest on the endothelium, transendothelial migration (TEM), followed by the invasion into the subendothelial extracellular matrix (ECM) of distant tissues. While cancer research has mostly focused on the biomechanical interactions between tumor cells (TCs) and ECM, particularly at the primary tumor site, very little is known about the mechanical properties of endothelial cells and the subendothelial ECM and how they contribute to the extravasation process. Here, an integrated experimental and theoretical framework is developed to investigate the mechanical crosstalk between TCs, endothelium and subendothelial ECM during in vitro cancer cell extravasation. It is found that cancer cell actin-rich protrusions generate complex push-pull forces to initiate and drive TEM, while transmigration success also relies on the forces generated by the endothelium. Consequently, mechanical properties of the subendothelial ECM and endothelial actomyosin contractility that mediate the endothelial forces also impact the endothelium's resistance to cancer cell transmigration. These results indicate that mechanical features of distant tissues, including force interactions between the endothelium and the subendothelial ECM, are key determinants of metastatic organotropism.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/348528
https://api.elsevier.com/content/abstract/scopus_id/85152548921
url http://hdl.handle.net/10261/348528
https://api.elsevier.com/content/abstract/scopus_id/85152548921
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI//RYC-2016-20352,
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-096778-A-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-128107OB-I00
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
The underlying dataset has been published as supplementary material of the article in the publisher platform at 10.1002/advs.202206554
https://doi.org/10.1002/advs.202206554
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
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