Cargando…
In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior
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 challengin...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448148/ https://www.ncbi.nlm.nih.gov/pubmed/26000481 http://dx.doi.org/10.1016/j.cell.2015.04.042 |
_version_ | 1782373659562737664 |
---|---|
author | Zomer, Anoek Maynard, Carrie Verweij, Frederik Johannes Kamermans, Alwin Schäfer, Ronny Beerling, Evelyne Schiffelers, Raymond Michel de Wit, Elzo Berenguer, Jordi Ellenbroek, Saskia Inge Johanna Wurdinger, Thomas Pegtel, Dirk Michiel van Rheenen, Jacco |
author_facet | Zomer, Anoek Maynard, Carrie Verweij, Frederik Johannes Kamermans, Alwin Schäfer, Ronny Beerling, Evelyne Schiffelers, Raymond Michel de Wit, Elzo Berenguer, Jordi Ellenbroek, Saskia Inge Johanna Wurdinger, Thomas Pegtel, Dirk Michiel van Rheenen, Jacco |
author_sort | Zomer, Anoek |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4448148 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44481482015-06-02 In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior Zomer, Anoek Maynard, Carrie Verweij, Frederik Johannes Kamermans, Alwin Schäfer, Ronny Beerling, Evelyne Schiffelers, Raymond Michel de Wit, Elzo Berenguer, Jordi Ellenbroek, Saskia Inge Johanna Wurdinger, Thomas Pegtel, Dirk Michiel van Rheenen, Jacco Cell Article 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. Cell Press 2015-05-21 /pmc/articles/PMC4448148/ /pubmed/26000481 http://dx.doi.org/10.1016/j.cell.2015.04.042 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zomer, Anoek Maynard, Carrie Verweij, Frederik Johannes Kamermans, Alwin Schäfer, Ronny Beerling, Evelyne Schiffelers, Raymond Michel de Wit, Elzo Berenguer, Jordi Ellenbroek, Saskia Inge Johanna Wurdinger, Thomas Pegtel, Dirk Michiel van Rheenen, Jacco In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior |
title | In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior |
title_full | In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior |
title_fullStr | In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior |
title_full_unstemmed | In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior |
title_short | In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior |
title_sort | in vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448148/ https://www.ncbi.nlm.nih.gov/pubmed/26000481 http://dx.doi.org/10.1016/j.cell.2015.04.042 |
work_keys_str_mv | AT zomeranoek invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior AT maynardcarrie invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior AT verweijfrederikjohannes invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior AT kamermansalwin invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior AT schaferronny invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior AT beerlingevelyne invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior AT schiffelersraymondmichel invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior AT dewitelzo invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior AT berenguerjordi invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior AT ellenbroeksaskiaingejohanna invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior AT wurdingerthomas invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior AT pegteldirkmichiel invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior AT vanrheenenjacco invivoimagingrevealsextracellularvesiclemediatedphenocopyingofmetastaticbehavior |