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In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior

Most cancer cells release heterogeneous populations of extracellular vesicles (EVs) containing proteins, lipids, and nucleic acids. In vitro experiments showed that EV uptake can lead to transfer of functional mRNA and altered cellular behavior. However, similar in vivo experiments remain challengin...

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Detalles Bibliográficos
Autores principales: Zomer, Anoek, Maynard, Carrie, Verweij, Frederik Johannes, Kamermans, Alwin, Schäfer, Ronny, Beerling, Evelyne, Schiffelers, Raymond Michel, de Wit, Elzo, Berenguer, Jordi, Ellenbroek, Saskia Inge Johanna, Wurdinger, Thomas, Pegtel, Dirk Michiel, van Rheenen, Jacco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448148/
https://www.ncbi.nlm.nih.gov/pubmed/26000481
http://dx.doi.org/10.1016/j.cell.2015.04.042
Descripción
Sumario:Most cancer cells release heterogeneous populations of extracellular vesicles (EVs) containing proteins, lipids, and nucleic acids. In vitro experiments showed that EV uptake can lead to transfer of functional mRNA and altered cellular behavior. However, similar in vivo experiments remain challenging because cells that take up EVs cannot be discriminated from non-EV-receiving cells. Here, we used the Cre-LoxP system to directly identify tumor cells that take up EVs in vivo. We show that EVs released by malignant tumor cells are taken up by less malignant tumor cells located within the same and within distant tumors and that these EVs carry mRNAs involved in migration and metastasis. By intravital imaging, we show that the less malignant tumor cells that take up EVs display enhanced migratory behavior and metastatic capacity. We postulate that tumor cells locally and systemically share molecules carried by EVs in vivo and that this affects cellular behavior.