Endothelial extracellular vesicles promote tumour growth by tumour‐associated macrophage reprogramming

Journal of Extracellular Vesicles

Julien Guiot¹  Souad Rahmouni²  Sophie Jacques²  Franck Dequiedt³  Tina O'Grady³  Michelle Lion³  Maureen Cambier⁴  Stephanie Herkenne⁴  Florian Muller⁴  Makon‐Sébastien Njock⁴  Ingrid Struman⁴  Claire Remacle⁴  Olivier Nivelles⁴  Aurélie Christian⁴ 

[1] Department of Pneumology GIGA Research Centre University and CHU of Liège Liège Belgium;Laboratory of Animal Genomics GIGA‐Medical Genomics GIGA Research Centre University of Liège Liège Belgium;Laboratory of Gene Expression and Cancer GIGA‐MBD University of Liège Liège Belgium;Laboratory of Molecular Angiogenesis GIGA Research Centre University of Liège Liège Belgium;

关键词: breast cancer;    extracellular vesicles;    macrophages;    microRNA;    TAM;   

DOI  :  10.1002/jev2.12228

来源: DOAJ

【 摘 要 】

Abstract Tumour‐derived extracellular vesicles (EVs) participate in tumour progression by deregulating various physiological processes including angiogenesis and inflammation. Here we report that EVs released by endothelial cells in a mammary tumour environment participate in the recruitment of macrophages within the tumour, leading to an immunomodulatory phenotype permissive for tumour growth. Using RNA‐Seq approaches, we identified several microRNAs (miRNAs) found in endothelial EVs sharing common targets involved in the regulation of the immune system. To further study the impact of these miRNAs in a mouse tumour model, we focused on three miRNAs that are conserved between humans and mouse, that is, miR‐142‐5p, miR‐183‐5p and miR‐222‐3p. These miRNAs are released from endothelial cells in a tumour microenvironment and are transferred via EVs to macrophages. In mouse mammary tumour models, treatment with EVs enriched in these miRNAs leads to a polarization of macrophages toward an M2‐like phenotype, which in turn promotes tumour growth.

【 授权许可】

Unknown