In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior
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Publication date
2015-05-21
Authors
Zomer, A. C.
Maynard, Carrie
Verweij, Frederik Johannes
Kamermans, Alwin
Schafer, Ronny
Beerling, Evelyne
Schiffelers, Raymond
de Wit, Elzo
Berenguer, Jordi
Ellenbroek, Saskia Inge Johanna
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Article
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Abstract
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.
Keywords
EXOSOMES, CANCER, CELLS, MICROVESICLES, MICROENVIRONMENT, HALLMARKS, PROGRESSION, BIOMARKERS, INVASION, TUMORS, Journal Article, Research Support, Non-U.S. Gov't
Citation
Zomer, A, Maynard, C, Verweij, F J, Kamermans, A, Schafer, R, Beerling, E, Schiffelers, R M, de Wit, E, Berenguer, J, Ellenbroek, S I J, Wurdinger, T, Pegtel, D M & van Rheenen, J 2015, 'In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior', Cell, vol. 161, no. 5, pp. 1046-1057. https://doi.org/10.1016/j.cell.2015.04.042