An article, titled Hemodynamic forces tune the arrest, adhesion and extravasation of circulating tumor cells, was published in the Developmental Cell journal (volume 45, issue 1, april 9 2018) on our collaboration with the team of Jacky Goetz from INSERM.
Un article a été publié dans le journal Developmental Cell (volume 45, issue 1, du 9 avril 2018) dans le cadre de notre collaboration avec l’équipe de Jacky Goetz (INSERM). Le titre de cet article est : Hemodynamic forces tune the arrest, adhesion and extravasation of circulating tumor cells.
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.
Altogether, these results demonstrate that hemodynamic profiles at metastatic sites regulate key steps of extravasation preceding metastatic outgrowth.
We would like to thank all our collaborators on this work.
This work has been funded by Plan Cancer, CNRS IMAG’IN, La Ligue Contre le Cancer, INSERM/Région Alsace, FRM (Fondation pour la Recherche Médicale), ANR (MONU-Vivabrain), the Labex IRMIA, institutional funds from INSERM and University of Strasbourg as well as by the Center of Modeling and Simulation of Strasbourg (CEMOSIS).