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Cell Rep. 2019 Sep 3;28(10):2491-2500.e5. doi: 10.1016/j.celrep.2019.07.102.

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

Author information

1
INSERM UMR_S1109, Tumor Biomechanics, Strasbourg 67000, France; Université de Strasbourg, Strasbourg 67000, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France.
2
INSERM UMR_S1109, Tumor Biomechanics, Strasbourg 67000, France; Université de Strasbourg, Strasbourg 67000, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France. Electronic address: harlepp@unistra.fr.
3
INSERM UMR_S1109, Tumor Biomechanics, Strasbourg 67000, France; Université de Strasbourg, Strasbourg 67000, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France. Electronic address: jacky.goetz@inserm.fr.

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.

KEYWORDS:

adhesion; arrest; biomechanics; circulating tumor cell; integrins; metastasis; zebrafish

PMID:
31484062
DOI:
10.1016/j.celrep.2019.07.102
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