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Dev Cell. 2019 Feb 25;48(4):554-572.e7. doi: 10.1016/j.devcel.2019.01.014. Epub 2019 Feb 7.

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

Author information

1
INSERM UMR_S1109, Strasbourg 67200, France; Université de Strasbourg, Strasbourg 67200, France; Fédération de Médecine Translationnelle de Strasbourg, Strasbourg 67200, France; CNRS SNC5055, Strasbourg 67200, France. Electronic address: hyenne@unistra.fr.
2
INSERM UMR_S1109, Strasbourg 67200, France; Université de Strasbourg, Strasbourg 67200, France; Fédération de Médecine Translationnelle de Strasbourg, Strasbourg 67200, France.
3
Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Université de Strasbourg, Illkirch 67000, France.
4
CNRS, Laboratoire de Spectrométrie de Masse Bio-Organique (LSMBO), IPHC, UMR 7178, Université de Strasbourg, Strasbourg 67087, France.
5
Electron Microscopy Core Facility, European Molecular Biology Laboratory, Heidelberg 69117, Germany.
6
Microenvironment and metastasis group. Department of Molecular Oncology, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
7
Institut Curie, PSL Research University, CNRS UMR144, Paris 75005, France; Center for Psychiatry and Neuroscience, Hôpital Saint-Anne, Université Descartes, INSERM U894, Paris 75014, France.
8
IRMB, Université de Montpellier, INSERM, Montpellier, France.
9
INSERM UMR_S1109, Strasbourg 67200, France; Université de Strasbourg, Strasbourg 67200, France; Fédération de Médecine Translationnelle de Strasbourg, Strasbourg 67200, France. Electronic address: jacky.goetz@inserm.fr.

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.

KEYWORDS:

correlated light and electron microscopy; exosomes; extracellular vesicles; patrolling macrophages; premetastatic niche; zebrafish

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