TY - JOUR
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
N1 - Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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 -