Javanmardi, Yousef;
Agrawal, Ayushi;
Malandrino, Andrea;
Lasli, Soufian;
Chen, Michelle;
Shahreza, Somayeh;
Serwinski, Bianca;
... Moeendarbary, Emad; + view all
(2023)
Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration.
Advanced Science
, Article e2206554. 10.1002/advs.202206554.
(In press).
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/advs.202206554 |
| Publisher version: | https://doi.org/10.1002/advs.202206554 |
| Language: | English |
| Additional information: | © 2023 The Authors. Advanced Science published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | biomaterial properties, cancer cell extravasation, computational modeling, metastasis, traction force microscopy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10168458 |
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