Cancer cell invasion alters the protein profile of extracellular vesicles

Abstract Extracellular vesicles (EVs) are important mediators of intercellular communication involved in local and long‐range signalling of cancer metastasis. The onset of invasion is the key step of the metastatic cascade, but the secretion of EVs has remained unexplored at that stage due to techni...

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Main Authors: Jens C. Luoto, Leila S. Coelho‐Rato, Cecilia Jungarå, Sara H. Bengs, Jannica Roininen, John E. Eriksson, Lea Sistonen, Eva Henriksson
Format: Article
Language:English
Published: Wiley 2023-12-01
Series:Journal of Extracellular Biology
Subjects:
Online Access:https://doi.org/10.1002/jex2.124
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author Jens C. Luoto
Leila S. Coelho‐Rato
Cecilia Jungarå
Sara H. Bengs
Jannica Roininen
John E. Eriksson
Lea Sistonen
Eva Henriksson
author_facet Jens C. Luoto
Leila S. Coelho‐Rato
Cecilia Jungarå
Sara H. Bengs
Jannica Roininen
John E. Eriksson
Lea Sistonen
Eva Henriksson
author_sort Jens C. Luoto
collection DOAJ
description Abstract Extracellular vesicles (EVs) are important mediators of intercellular communication involved in local and long‐range signalling of cancer metastasis. The onset of invasion is the key step of the metastatic cascade, but the secretion of EVs has remained unexplored at that stage due to technical challenges. In this study, we present a platform to track EVs over the course of invasive development of human prostate cancer cell (PC3) tumoroids utilizing in vivo‐mimicking extracellular matrix‐based 3D cultures. Using this EV production method, combined with proteomic profiling, we show that PC3 tumoroids secrete EVs with previously undefined protein cargo. Intriguingly, an increase in EV amounts and extensive changes in the EV protein composition were detected upon invasive transition of the tumoroids. The changes in EV protein cargo were counteracted by chemical inhibition of invasion. These results reveal the impact of the tumoroids’ invasive status on EV secretion and cargo, and highlight the necessity of in vivo‐mimicking conditions for uncovering novel cancer‐derived EV components.
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spelling doaj.art-76eca7fb0c87468bb4c873159fc6b3822023-12-21T07:04:28ZengWileyJournal of Extracellular Biology2768-28112023-12-01212n/an/a10.1002/jex2.124Cancer cell invasion alters the protein profile of extracellular vesiclesJens C. Luoto0Leila S. Coelho‐Rato1Cecilia Jungarå2Sara H. Bengs3Jannica Roininen4John E. Eriksson5Lea Sistonen6Eva Henriksson7Faculty of Science and Engineering, Cell Biology Åbo Akademi University Turku FinlandFaculty of Science and Engineering, Cell Biology Åbo Akademi University Turku FinlandFaculty of Science and Engineering, Cell Biology Åbo Akademi University Turku FinlandFaculty of Science and Engineering, Cell Biology Åbo Akademi University Turku FinlandFaculty of Science and Engineering, Cell Biology Åbo Akademi University Turku FinlandFaculty of Science and Engineering, Cell Biology Åbo Akademi University Turku FinlandFaculty of Science and Engineering, Cell Biology Åbo Akademi University Turku FinlandFaculty of Science and Engineering, Cell Biology Åbo Akademi University Turku FinlandAbstract Extracellular vesicles (EVs) are important mediators of intercellular communication involved in local and long‐range signalling of cancer metastasis. The onset of invasion is the key step of the metastatic cascade, but the secretion of EVs has remained unexplored at that stage due to technical challenges. In this study, we present a platform to track EVs over the course of invasive development of human prostate cancer cell (PC3) tumoroids utilizing in vivo‐mimicking extracellular matrix‐based 3D cultures. Using this EV production method, combined with proteomic profiling, we show that PC3 tumoroids secrete EVs with previously undefined protein cargo. Intriguingly, an increase in EV amounts and extensive changes in the EV protein composition were detected upon invasive transition of the tumoroids. The changes in EV protein cargo were counteracted by chemical inhibition of invasion. These results reveal the impact of the tumoroids’ invasive status on EV secretion and cargo, and highlight the necessity of in vivo‐mimicking conditions for uncovering novel cancer‐derived EV components.https://doi.org/10.1002/jex2.1243D culturesEV heterogeneityEV proteomeextracellular vesiclesinvasionPC3 cells
spellingShingle Jens C. Luoto
Leila S. Coelho‐Rato
Cecilia Jungarå
Sara H. Bengs
Jannica Roininen
John E. Eriksson
Lea Sistonen
Eva Henriksson
Cancer cell invasion alters the protein profile of extracellular vesicles
Journal of Extracellular Biology
3D cultures
EV heterogeneity
EV proteome
extracellular vesicles
invasion
PC3 cells
title Cancer cell invasion alters the protein profile of extracellular vesicles
title_full Cancer cell invasion alters the protein profile of extracellular vesicles
title_fullStr Cancer cell invasion alters the protein profile of extracellular vesicles
title_full_unstemmed Cancer cell invasion alters the protein profile of extracellular vesicles
title_short Cancer cell invasion alters the protein profile of extracellular vesicles
title_sort cancer cell invasion alters the protein profile of extracellular vesicles
topic 3D cultures
EV heterogeneity
EV proteome
extracellular vesicles
invasion
PC3 cells
url https://doi.org/10.1002/jex2.124
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