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.
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Anoek
authors.initials: A
authors.lastname: Zomer
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Carrie
authors.initials: C
authors.lastname: Maynard
authors.affiliation: Department of Pathology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Frederik Johannes
authors.initials: FJ
authors.lastname: Verweij
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Alwin
authors.initials: A
authors.lastname: Kamermans
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Ronny
authors.initials: R
authors.lastname: Schäfer
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Beerling
authors.affiliation: Laboratory Clinical Chemistry & Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
authors.forename: Raymond Michel
authors.initials: RM
authors.lastname: Schiffelers
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Elzo
authors.initials: E
authors.lastname: de Wit
authors.affiliation: Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Jordi
authors.initials: J
authors.lastname: Berenguer
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Saskia Inge Johanna
authors.initials: SIJ
authors.lastname: Ellenbroek
authors.affiliation: Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wurdinger
authors.affiliation: Department of Pathology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Dirk Michiel
authors.initials: DM
authors.lastname: Pegtel
authors.affiliation: Cancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands. Electronic address: j.vanrheenen@hubrecht.eu.
authors.forename: Jacco
authors.initials: J
authors.lastname: van Rheenen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D019426:Integrases / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: C045073:Cre recombinase; D019426:Integrases