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, Nicolas, Spill, Fabian, Bertazzo, Sergio, Sheridan, Graham K, Shenoy, Vivek, Calvo González, Fernando|||0000-0001-8858-1185, Kamm, Roger, Moeendarbary, Emad
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/30083
Acceso en línea:https://hdl.handle.net/10902/30083
Access Level:acceso abierto
Palabra clave:Biomaterial properties
Cancer cell extravasation
Computational modeling
Metastasis
Traction force microscopy
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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, NicolasSpill, FabianBertazzo, SergioSheridan, Graham KShenoy, VivekCalvo González, Fernando|||0000-0001-8858-1185Kamm, RogerMoeendarbary, EmadBiomaterial propertiesCancer cell extravasationComputational modelingMetastasisTraction force microscopyCancer 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 organotropismAcknowledgements: The authors would like to thank all members of the RK and EM Laboratories as well as Erik Sahai (Francis Crick Institute) for critical discussions and support. 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)WileyUniversidad de Cantabria20232023-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/30083Advanced Science, 2023, 10(16), 2206554reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/300832026-06-02T12:39:31Z
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
Biomaterial properties
Cancer cell extravasation
Computational modeling
Metastasis
Traction force microscopy
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, Nicolas
Spill, Fabian
Bertazzo, Sergio
Sheridan, Graham K
Shenoy, Vivek
Calvo González, Fernando|||0000-0001-8858-1185
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, Nicolas
Spill, Fabian
Bertazzo, Sergio
Sheridan, Graham K
Shenoy, Vivek
Calvo González, Fernando|||0000-0001-8858-1185
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, Nicolas
Spill, Fabian
Bertazzo, Sergio
Sheridan, Graham K
Shenoy, Vivek
Calvo González, Fernando|||0000-0001-8858-1185
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 Universidad de Cantabria
dc.subject.none.fl_str_mv Biomaterial properties
Cancer cell extravasation
Computational modeling
Metastasis
Traction force microscopy
topic Biomaterial properties
Cancer cell extravasation
Computational modeling
Metastasis
Traction force microscopy
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
2023-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10902/30083
url https://hdl.handle.net/10902/30083
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Advanced Science, 2023, 10(16), 2206554
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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