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

被引：169

作者：

Hyenne, Vincent ^{[1
,2
,3
,4
]}

Ghoroghi, Shima ^{[1
,2
,3
]}

Collot, Mayeul ^{[5
]}

Bons, Joanna ^{[6
]}

Follain, Gautier ^{[1
,2
,3
]}

Harlepp, Sebastien ^{[1
,2
,3
]}

Mary, Benjamin ^{[1
,2
,3
]}

Bauer, Jack ^{[1
,2
,3
]}

Mercier, Luc ^{[1
,2
,3
]}

Busnelli, Ignacio ^{[1
,2
,3
]}

Lefebvre, Olivier ^{[1
,2
,3
]}

Fekonja, Nina ^{[1
,2
,3
]}

Garcia-Leon, Maria J. ^{[1
,2
,3
]}

Machado, Pedro ^{[7
]}

Delalande, Francois ^{[6
]}

Amor Lopez, Ana ^{[8
]}

Garcia Silva, Susana ^{[8
]}

Verweij, Frederik J. ^{[9
,10
]}

van Niel, Guillaume ^{[9
,10
]}

Djouad, Farida ^{[11
]}

Peinado, Hector ^{[8
]}

Carapito, Christine ^{[6
]}

Klymchenko, Andrey S. ^{[5
]}

Goetz, Jacky G. ^{[1
,2
,3
]}

机构：

[1] INSERM UMR S1109, F-67200 Strasbourg, France

[2] Univ Strasbourg, F-67200 Strasbourg, France

[3] Fed Med Translat Strasbourg, F-67200 Strasbourg, France

[4] CNRS SNC5055, F-67200 Strasbourg, France

[5] Univ Strasbourg, UMR CNRS 7213, Lab Biophoton & Pharmacol, F-67000 Illkirch Graffenstaden, France

[6] Univ Strasbourg, CNRS, UMR 7178, LSMBO,IPHC, F-67087 Strasbourg, France

[7] European Mol Biol Lab, Electron Microscopy Core Facil, D-69117 Heidelberg, Germany

[8] Spanish Natl Canc Res Ctr CNIO, Dept Mol Oncol, Microenvironm & Metastasis Grp, Madrid, Spain

[9] PSL Res Univ, Inst Curie, CNRS UMR144, F-75005 Paris, France

[10] Univ Descartes, Hop St Anne, Ctr Psychiat & Neurosci, INSERM U894, F-75014 Paris, France

[11] Univ Montpellier, INSERM, IRMB, Montpellier, France

来源：

DEVELOPMENTAL CELL | 2019年 / 48卷 / 04期

关键词：

METASTATIC NICHE FORMATION; IN-VIVO; B16BL6-DERIVED EXOSOMES; CELLS; CANCER; MICROVESICLES; VISUALIZATION; MONOCYTES; BLOOD; EXTRAVASATION;

D O I：

10.1016/j.devcel.2019.01.014

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：554 / +

页数：26

共 79 条

[1] Intercellular transfer of the oncogenic receptor EGFrvIII by microvesicles derived from tumour cells [J].