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Metastatic Tumor Cells Exploit Their Adhesion Repertoire to Counteract Shear Forces during Intravascular Arrest.

Authors :
Osmani N
Follain G
García León MJ
Lefebvre O
Busnelli I
Larnicol A
Harlepp S
Goetz JG
Source :
Cell reports [Cell Rep] 2019 Sep 03; Vol. 28 (10), pp. 2491-2500.e5.
Publication Year :
2019

Abstract

Cancer metastasis is a process whereby a primary tumor spreads to distant organs. We have demonstrated previously that blood flow controls the intravascular arrest of circulating tumor cells (CTCs) through stable adhesion to endothelial cells. We now aim to define the contribution of cell adhesion potential and identify adhesion receptors at play. Early arrest is mediated by the formation of weak adhesion, depending on CD44 and integrin αvβ3. Stabilization of this arrest uses integrin α5β1-dependent adhesions with higher adhesion strength, which allows CTCs to stop in vascular regions with lower shear forces. Moreover, blood flow favors luminal deposition of fibronectin on endothelial cells, an integrin α5β1 ligand. Finally, we show that only receptors involved in stable adhesion are required for subsequent extravasation and metastasis. In conclusion, we identified the molecular partners that are sequentially exploited by CTCs to arrest and extravasate in vascular regions with permissive flow regimes.<br /> (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
2211-1247
Volume :
28
Issue :
10
Database :
MEDLINE
Journal :
Cell reports
Publication Type :
Academic Journal
Accession number :
31484062
Full Text :
https://doi.org/10.1016/j.celrep.2019.07.102