Graphical Abstract Highlights d MemBright allows for bright and specific staining of EVs d The zebrafish embryo allows tracking of tumor EVs at high spatiotemporal resolution d Circulating tumor EVs are mostly taken up by endothelial cells and patrolling macrophages d Zebrafish melanoma EVs favor metastatic outgrowth in zebrafish embryos
Cancer extracellular vesicles (EVs) shuttle at distance and fertilize pre-metastatic niches facilitating subsequent seeding by tumor cells. However, the link between EV secretion mechanisms and their capacity to form pre-metastatic niches remains obscure. Using mouse models, we show that GTPases of the Ral family control, through the phospholipase D1, multi-vesicular bodies homeostasis and tune the biogenesis and secretion of pro-metastatic EVs. Importantly, EVs from RalA or RalB depleted cells have limited organotropic capacities in vivoand are less efficient in promoting metastasis. RalA and RalB reduce the EV levels of the adhesion molecule MCAM/CD146, which favors EV-mediated metastasis by allowing EVs targeting to the lungs. Finally, RalA, RalB, and MCAM/CD146, are factors of poor prognosis in breast cancer patients. Altogether, our study identifies RalGTPases as central molecules linking the mechanisms of EVs secretion and cargo loading to their capacity to disseminate and induce pre-metastatic niches in a CD146-dependent manner.
Aims The flow of electric current in the root-soil system relates to the pathways of water and solutes, its characterization provides information on the root architecture and functioning. We developed a current source density approach with the goal of non-invasively image the current pathways in the root-soil system. Methods A current flow is applied from the plant stem to the soil, the proposed geoelectrical approach images the resulting distribution and intensity of the electric current in the root-soil system. The numerical inversion procedure underlying the approach was tested in numer
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