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

doi:10.1016/j.cell.2015.04.042

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

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.

Original language	English
Pages (from-to)	1046-57
Number of pages	12
Journal	Cell
Volume	161
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2015.04.042
Publication status	Published - 21 May 2015

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title = "In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior",

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.",

author = "Anoek Zomer and Carrie Maynard and Verweij, {Frederik Johannes} and Alwin Kamermans and Ronny Sch{\"a}fer and Evelyne Beerling and Schiffelers, {Raymond Michel} and {de Wit}, Elzo and Jordi Berenguer and Ellenbroek, {Saskia Inge Johanna} and Thomas Wurdinger and Pegtel, {Dirk Michiel} and {van Rheenen}, Jacco",

year = "2015",

month = may,

day = "21",

doi = "10.1016/j.cell.2015.04.042",

language = "English",

volume = "161",

pages = "1046--57",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "5",

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T1 - In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior

AU - Zomer, Anoek

AU - Maynard, Carrie

AU - Verweij, Frederik Johannes

AU - Kamermans, Alwin

AU - Schäfer, Ronny

AU - Beerling, Evelyne

AU - Schiffelers, Raymond Michel

AU - de Wit, Elzo

AU - Berenguer, Jordi

AU - Ellenbroek, Saskia Inge Johanna

AU - Wurdinger, Thomas

AU - Pegtel, Dirk Michiel

AU - van Rheenen, Jacco

PY - 2015/5/21

Y1 - 2015/5/21

N2 - 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.

AB - 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.

U2 - 10.1016/j.cell.2015.04.042

DO - 10.1016/j.cell.2015.04.042

M3 - Article

C2 - 26000481

SN - 0092-8674

VL - 161

SP - 1046

EP - 1057

JO - Cell

JF - Cell

IS - 5

ER -

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

Abstract

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