Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration

Yousef Javanmardi, Ayushi Agrawal, Andrea Malandrino, Soufian Lasli, Michelle Chen, Somayeh Shahreza, Bianca Serwinski, Leila Cammoun, Ran Li, Mehdi Jorfi, Boris Djordjevic, Nicolas Szita, Fabian Spill, Sergio Bertazzo, Graham K Sheridan, Vivek Shenoy, Fernando Calvo*, Roger Kamm*, Emad Moeendarbary*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.
Original languageEnglish
Article number2206554
JournalAdvanced Science
Early online date13 Apr 2023
DOIs
Publication statusE-pub ahead of print - 13 Apr 2023

Bibliographical note

© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

Keywords

  • biomaterial properties
  • cancer cell extravasation
  • computational modeling
  • metastasis
  • traction force microscopy
  • Research Articles
  • Research Article

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