Homosalate boosts the release of tumour‐derived extracellular vesicles with protection against anchorage‐loss property

Abstract Eukaryotic cells, including cancer cells, secrete highly heterogeneous populations of extracellular vesicles (EVs). EVs could have different subcellular origin, composition and functional properties, but tools to distinguish between EV subtypes are scarce. Here, we tagged CD63‐ or CD9‐posit...

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Main Authors: Eleonora Grisard, Nathalie Nevo, Aurianne Lescure, Sebastian Doll, Maxime Corbé, Mabel Jouve, Gregory Lavieu, Alain Joliot, Elaine Del Nery, Lorena Martin‐Jaular, Clotilde Théry
Format: Article
Language:English
Published: Wiley 2022-07-01
Series:Journal of Extracellular Vesicles
Online Access:https://doi.org/10.1002/jev2.12242
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author Eleonora Grisard
Nathalie Nevo
Aurianne Lescure
Sebastian Doll
Maxime Corbé
Mabel Jouve
Gregory Lavieu
Alain Joliot
Elaine Del Nery
Lorena Martin‐Jaular
Clotilde Théry
author_facet Eleonora Grisard
Nathalie Nevo
Aurianne Lescure
Sebastian Doll
Maxime Corbé
Mabel Jouve
Gregory Lavieu
Alain Joliot
Elaine Del Nery
Lorena Martin‐Jaular
Clotilde Théry
author_sort Eleonora Grisard
collection DOAJ
description Abstract Eukaryotic cells, including cancer cells, secrete highly heterogeneous populations of extracellular vesicles (EVs). EVs could have different subcellular origin, composition and functional properties, but tools to distinguish between EV subtypes are scarce. Here, we tagged CD63‐ or CD9‐positive EVs secreted by triple negative breast cancer cells with Nanoluciferase enzyme, to set‐up a miniaturized method to quantify secretion of these two EV subtypes directly in the supernatant of cells. We performed a cell‐based high‐content screening to identify clinically‐approved drugs able to affect EV secretion. One of the identified hits is Homosalate, an anti‐inflammatory drug found in sunscreens which robustly increased EVs’ release. Comparing EVs induced by Homosalate with those induced by Bafilomycin A1, we demonstrate that: (1) the two drugs act on EVs generated in distinct subcellular compartments, and (2) EVs released by Homosalate‐, but not by Bafilomycin A1‐treated cells enhance resistance to anchorage loss in another recipient epithelial tumour cell line. In conclusion, we identified a new drug modifying EV release and demonstrated that under influence of different drugs, triple negative breast cancer cells release EV subpopulations from different subcellular origins harbouring distinct functional properties.
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spelling doaj.art-1595545f8d25444cabe89f29779efd302023-02-07T09:01:22ZengWileyJournal of Extracellular Vesicles2001-30782022-07-01117n/an/a10.1002/jev2.12242Homosalate boosts the release of tumour‐derived extracellular vesicles with protection against anchorage‐loss propertyEleonora Grisard0Nathalie Nevo1Aurianne Lescure2Sebastian Doll3Maxime Corbé4Mabel Jouve5Gregory Lavieu6Alain Joliot7Elaine Del Nery8Lorena Martin‐Jaular9Clotilde Théry10Institut Curie PSL Research University INSERM U932 Paris FranceInstitut Curie PSL Research University INSERM U932 Paris FranceInstitut Curie PSL Research University, Translational Research Department, BioPhenics Platform PICT‐IBISA Paris FranceInstitute of Metabolism and Cell Death Helmholtz Zentrum München Neuherberg GermanyInstitut Curie PSL Research University, Translational Research Department, BioPhenics Platform PICT‐IBISA Paris FranceInstitut Curie PSL Research University CNRS UMR3215 Paris FranceInstitut Curie PSL Research University INSERM U932 Paris FranceInstitut Curie PSL Research University INSERM U932 Paris FranceInstitut Curie PSL Research University, Translational Research Department, BioPhenics Platform PICT‐IBISA Paris FranceInstitut Curie PSL Research University INSERM U932 Paris FranceInstitut Curie PSL Research University INSERM U932 Paris FranceAbstract Eukaryotic cells, including cancer cells, secrete highly heterogeneous populations of extracellular vesicles (EVs). EVs could have different subcellular origin, composition and functional properties, but tools to distinguish between EV subtypes are scarce. Here, we tagged CD63‐ or CD9‐positive EVs secreted by triple negative breast cancer cells with Nanoluciferase enzyme, to set‐up a miniaturized method to quantify secretion of these two EV subtypes directly in the supernatant of cells. We performed a cell‐based high‐content screening to identify clinically‐approved drugs able to affect EV secretion. One of the identified hits is Homosalate, an anti‐inflammatory drug found in sunscreens which robustly increased EVs’ release. Comparing EVs induced by Homosalate with those induced by Bafilomycin A1, we demonstrate that: (1) the two drugs act on EVs generated in distinct subcellular compartments, and (2) EVs released by Homosalate‐, but not by Bafilomycin A1‐treated cells enhance resistance to anchorage loss in another recipient epithelial tumour cell line. In conclusion, we identified a new drug modifying EV release and demonstrated that under influence of different drugs, triple negative breast cancer cells release EV subpopulations from different subcellular origins harbouring distinct functional properties.https://doi.org/10.1002/jev2.12242
spellingShingle Eleonora Grisard
Nathalie Nevo
Aurianne Lescure
Sebastian Doll
Maxime Corbé
Mabel Jouve
Gregory Lavieu
Alain Joliot
Elaine Del Nery
Lorena Martin‐Jaular
Clotilde Théry
Homosalate boosts the release of tumour‐derived extracellular vesicles with protection against anchorage‐loss property
Journal of Extracellular Vesicles
title Homosalate boosts the release of tumour‐derived extracellular vesicles with protection against anchorage‐loss property
title_full Homosalate boosts the release of tumour‐derived extracellular vesicles with protection against anchorage‐loss property
title_fullStr Homosalate boosts the release of tumour‐derived extracellular vesicles with protection against anchorage‐loss property
title_full_unstemmed Homosalate boosts the release of tumour‐derived extracellular vesicles with protection against anchorage‐loss property
title_short Homosalate boosts the release of tumour‐derived extracellular vesicles with protection against anchorage‐loss property
title_sort homosalate boosts the release of tumour derived extracellular vesicles with protection against anchorage loss property
url https://doi.org/10.1002/jev2.12242
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