Fate and function of tumor extracellular vesicles in vivo
Extracellular vesicles (EVs), including exosomes, have emerged as novel mediators of cell/cell communication in multiple biological and pathological contexts. They are produced by all cell types, present in every body fluid and contain proteins and RNA (coding and non coding) able to change the phenotype of their receiving cell. Despite their increasing importance, their biogenesis, their dispersion and their function remain poorly understood. My work focuses on these aspects, using different animal models and favouring in vivo studies, intravital imaging and correlated light and electron microscopy. Over the past years, I used C. elegans to identify new genes involved in exosome biogenesis and secretion, and described the function of one of them, the RAL-1 GTPase (Hyenne et al. JCB 2015). We further show that mammalian RalA and RalB control EV levels, content and function in mouse mammary carcinoma, and that it could contribute to primary tumor growth and metastasis formation (unpublished data). In parallel, we developed the use of zebrafish as a novel animal model to track circulating EVs in a living organism at high temporal and spatial resolution (Hyenne et al. Dev. Cell 2019). We provided the first description of tumor EVs’ hemodynamic behavior and documented their intravascular arrest. We showed that circulating tumor EVs are rapidly taken up by endothelial cells and blood patrolling macrophages and subsequently stored in degradative compartments. Finally, we demonstrated that tumor EVs activate macrophages and promote metastatic outgrowth.
Tumor Biomechanics - INSERM UMR_S 1109 - Institut dhématologie et d'immunologie, Strasbourg
Domain 4 - UMR 144 - Subcellular Structure and Cellular Dynamics