Hemodynamic Forces Tune the Arrest, Adhesion, and Extravasation of Circulating Tumor Cells

Publication date: 9 April 2018
Source:Developmental Cell, Volume 45, Issue 1
Author(s): Gautier Follain, Naël Osmani, Ana Sofia Azevedo, Guillaume Allio, Luc Mercier, Matthia A. Karreman, Gergely Solecki, Marìa Jesùs Garcia Leòn, Olivier Lefebvre, Nina Fekonja, Claudia Hille, Vincent Chabannes, Guillaume Dollé, Thibaut Metivet, François Der Hovsepian, Christophe Prudhomme, Angélique Pichot, Nicodème Paul, Raphaël Carapito, Siamak Bahram, Bernhard Ruthensteiner, André Kemmling, Susanne Siemonsen, Tanja Schneider, Jens Fiehler, Markus Glatzel, Frank Winkler, Yannick Schwab, Klaus Pantel, Sébastien Harlepp, Jacky G. Goetz
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.

Graphical abstract

Teaser

Follain et al. demonstrate that blood flow forces tune both the arrest and extravasation of circulating tumor cells in vivo. Permissive flow forces allow stable intravascular arrest of circulating tumor cells. Flow forces drive endothelial remodeling around arrested tumor cells, favoring extravasation preceding metastatic outgrowth.


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