RT Journal Article
SR Electronic
T1 Studying the fate of tumor extracellular vesicles at high spatio-temporal resolution using the zebrafish embryo
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 380238
DO 10.1101/380238
A1 Vincent Hyenne
A1 Shima Ghoroghi
A1 Mayeul Collot
A1 Sébastien Harlepp
A1 Jack Bauer
A1 Luc Mercier
A1 Ignacio Busnelli
A1 Olivier Lefebvre
A1 Nina Fekonja
A1 Pedro Machado
A1 Joanna Bons
A1 François Delalande
A1 Ana Isabel Amor
A1 Susana Garcia Silva
A1 Frederik J. Verweij
A1 Guillaume Van Niel
A1 Yannick Schwab
A1 Héctor Peinado
A1 Christine Carapito
A1 Andrey S. Klymchenko
A1 Jacky G. Goetz
YR 2018
UL http://biorxiv.org/content/early/2018/07/30/380238.abstract
AB Tumor extracellular vesicles (tumor EVs) mediate the communication between tumor and stromal cells mostly to the benefit of tumor progression. Notably, tumor EVs have been reported to travel in the blood circulation, reach specific distant organs and locally modify the microenvironment. However, visualizing these events in vivo still faces major hurdles. Here, we show a new method for tracking individual circulating tumor EVs in a living organism: we combine novel, bright and specific fluorescent membrane probes, MemBright, with the transparent zebrafish embryo as an animal model. We provide the first description of tumor EVs’ hemodynamic behavior and document their arrest before internalization. Using transgenic lines, we show that circulating tumor EVs are uptaken by endothelial cells and blood patrolling macrophages, but not by leukocytes, and subsequently stored in acidic degradative compartments. Finally, we prove that the MemBright can be used to follow naturally released tumor EVs in vivo. Overall, our study demonstrates the usefulness and prospects of zebrafish embryo to track tumor EVs in vivo.HighlightsMemBright, a new family of membrane probes, allows for bright and specific staining of EVsZebrafish melanoma EVs are very similar to human and mouse melanoma EVs in morphology and protein contentThe zebrafish embryo is an adapted model to precisely track tumor EVs dynamics and fate in a living organism from light to electron microscopyCirculating tumor EVs are rapidly uptaken by endothelial cells and patrolling macrophagesCorrelated light and electron microscopy can be used in zebrafish to identify cells and compartments uptaking tumor EVsBlurb Dispersion of tumor extracellular vesicles (EVs) throughout the body promotes tumor progression. However the behavior of tumor EVs in body fluids remains mysterious due to their small size and the absence of adapted animal model. Here we show that the zebrafish embryo can be used to track circulating tumor EVs in vivo and provide the first high-resolution description of their dissemination and uptake.