In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior

Anoek Zomer, Carrie Maynard, Frederik Johannes Verweij, Alwin Kamermans, Ronny Schäfer, Evelyne Beerling, Raymond Michel Schiffelers, Elzo de Wit, Jordi Berenguer, Saskia Inge Johanna Ellenbroek, Thomas Wurdinger, Dirk Michiel Pegtel, Jacco van Rheenen

Research output: Contribution to journal/periodicalArticleScientificpeer-review


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.

Original languageEnglish
Pages (from-to)1046-57
Number of pages12
Issue number5
Publication statusPublished - 21 May 2015


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