PUBLICATION

Studying the Fate of Tumor Extracellular Vesicles at High Spatiotemporal Resolution Using the Zebrafish Embryo

Authors
Hyenne, V., Ghoroghi, S., Collot, M., Bons, J., Follain, G., Harlepp, S., Mary, B., Bauer, J., Mercier, L., Busnelli, I., Lefebvre, O., Fekonja, N., Garcia-Leon, M.J., Machado, P., Delalande, F., López, A.A., Silva, S.G., Verweij, F.J., van Niel, G., Djouad, F., Peinado, H., Carapito, C., Klymchenko, A.S., Goetz, J.G.
ID
ZDB-PUB-190213-2
Date
2019
Source
Developmental Cell   48(4): 554-572.e7 (Journal)
Registered Authors
Djouad, Farida
Keywords
correlated light and electron microscopy, exosomes, extracellular vesicles, patrolling macrophages, premetastatic niche, zebrafish
MeSH Terms
  • Animals
  • Cell Communication/physiology
  • Disease Models, Animal
  • Disease Progression
  • Endothelial Cells/cytology*
  • Exosomes/metabolism
  • Extracellular Vesicles/metabolism*
  • Neoplasms/pathology*
  • Stromal Cells/metabolism
  • Tumor Microenvironment/physiology*
  • Zebrafish
PubMed
30745140 Full text @ Dev. Cell
Abstract
Tumor extracellular vesicles (EVs) mediate the communication between tumor and stromal cells mostly to the benefit of tumor progression. Notably, tumor EVs travel in the bloodstream, reach distant organs, and locally modify the microenvironment. However, visualizing these events in vivo still faces major hurdles. Here, we describe an approach for tracking circulating tumor EVs in a living organism: we combine chemical and genetically encoded probes with the zebrafish embryo as an animal model. We provide a first description of tumor EVs' hemodynamic behavior and document their intravascular arrest. We show that circulating tumor EVs are rapidly taken up by endothelial cells and blood patrolling macrophages and subsequently stored in degradative compartments. Finally, we demonstrate that tumor EVs activate macrophages and promote metastatic outgrowth. Overall, our study proves the usefulness and prospects of zebrafish embryo to track tumor EVs and dissect their role in metastatic niches formation in vivo.
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