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

• Published in: Developmental cell Vol. 45; no. 1; pp. 33 - 52.e12
• Main Authors: Follain, Gautier, Osmani, Naël, Azevedo, Ana Sofia, Allio, Guillaume, Mercier, Luc, Karreman, Matthia A., Solecki, Gergely, Garcia Leòn, Marìa Jesùs, Lefebvre, Olivier, Fekonja, Nina, Hille, Claudia, Chabannes, Vincent, Dollé, Guillaume, Metivet, Thibaut, Hovsepian, François Der, Prudhomme, Christophe, Pichot, Angélique, Paul, Nicodème, Carapito, Raphaël, Bahram, Siamak, Ruthensteiner, Bernhard, Kemmling, André, Siemonsen, Susanne, Schneider, Tanja, Fiehler, Jens, Glatzel, Markus, Winkler, Frank, Schwab, Yannick, Pantel, Klaus, Harlepp, Sébastien, Goetz, Jacky G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.04.2018; Elsevier
• Subjects: biomechanics; blood flow; Cancer; cell adhesion; circulating tumor cells; Computer Science; endothelial remodeling; extravasation; Life Sciences; metastasis; Modeling and Simulation; zebrafish; extravasation; metastasis; endothelial remodeling; cell adhesion; biomechanics; zebrafish; circulating tumor cells; blood flow
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2018.02.015

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. [Display omitted] •Arrest of circulating tumor cells occurs in blood vessels with permissive flow profiles•pN-range adhesion forces favor rapid and stable intravascular adhesion•Flow-mediated endothelial remodeling drives extravasation of tumor cells 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.