Hemodynamic Forces Tune the Arrest, Adhesion, and Extravasation of Circulating Tumor Cells.
Fiche publication
Date publication
avril 2018
Journal
Developmental cell
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak, Dr LEFEBVRE Olivier, Dr CARAPITO Raphaël, Dr HARLEPP Sébastien, Dr OSMANI Naël
Tous les auteurs :
Follain G, Osmani N, Azevedo AS, Allio G, Mercier L, Karreman MA, Solecki G, Garcia Leòn MJ, Lefebvre O, Fekonja N, Hille C, Chabannes V, Dollé G, Metivet T, Hovsepian F, Prudhomme C, Pichot A, Paul N, Carapito R, Bahram S, Ruthensteiner B, Kemmling A, Siemonsen S, Schneider T, Fiehler J, Glatzel M, Winkler F, Schwab Y, Pantel K, Harlepp S, Goetz JG
Lien Pubmed
Résumé
Metastatic seeding is driven by cell-intrinsic and environmental cues, yet the contribution of biomechanics is poorly known. We aim to elucidate the impact of blood flow on the arrest and the extravasation of circulating tumor cells (CTCs) in vivo. Using the zebrafish embryo, we show that arrest of CTCs occurs in vessels with favorable flow profiles where flow forces control the adhesion efficacy of CTCs to the endothelium. We biophysically identified the threshold values of flow and adhesion forces allowing successful arrest of CTCs. In addition, flow forces fine-tune tumor cell extravasation by impairing the remodeling properties of the endothelium. Importantly, we also observe endothelial remodeling at arrest sites of CTCs in mouse brain capillaries. Finally, we observed that human supratentorial brain metastases preferably develop in areas with low perfusion. These results demonstrate that hemodynamic profiles at metastatic sites regulate key steps of extravasation preceding metastatic outgrowth.
Mots clés
biomechanics, blood flow, cell adhesion, circulating tumor cells, endothelial remodeling, extravasation, metastasis, zebrafish
Référence
Dev. Cell. 2018 Apr 9;45(1):33-52.e12