Endothelial calcium firing mediates the extravasation of metastatic tumor cells
Year: 2024
Type: article
Abstract: ABSTRACT Metastatic dissemination is driven by genetical, biochemical and biophysical cues that favor the distant colonization of organs and the formation of life-threatening secondary tumors. We have previously demonstrated that endothelial cells (ECs) actively remodel during extravasation by enwrapping arrested tumor cells (TCs) and extrude them from the vascular lumen while maintaining perfusion. In this work, we dissect the cellular and molecular mechanisms driving endothelial remodeling. Using high-resolution intravital imaging in zebrafish embryos, we demonstrate that the actomyosin network of ECs controls tissue remodeling and subsequent TC extravasation. Furthermore, we uncovered that this cytoskeletal remodeling is driven by altered endothelial- calcium (Ca 2+ ) signaling caused by arrested TCs. Accordingly, we demonstrated that inhibition of voltage-dependent calcium L-type channels impairs extravasation. Lastly, we identified P2X4, TRP, and Piezo1 mechano-gated Ca 2+ channels as key mediators of the process. These results further highlight the central role of endothelial remodeling during extravasation of TCs and open avenues for successful therapeutic targeting. Graphical Abstract
Source: iScience
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,150
Funders: Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation, Alliance Nationale pour les Sciences de la Vie et de la Santé, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Université de Strasbourg, Ligue Contre le Cancer, Centre National de la Recherche Scientifique, Institut National Du Cancer, Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation, National Cancer Institute, H2020 European Research Council
Awards: G164444715, Par-delà les frontières, l'Université de Strasbourg, From pathobioLogy to synoviA on chip: driving rheuMatoId arthritis to the precisioN medicine GOal, G2255650664, G2694206344, Façonner les talents en formation et en recherche à l'Université de Strasbourg, G3357951378, G3469731186, G399734812, G434337789, G471331628, G4779185514, G5247101237, G6136357505, G6276897512, G7240651115
OpenAlex ID: W4405807639