A1 Refereed original research article in a scientific journal
Cancer cell invasion alters the protein profile of extracellular vesicles
Authors: Luoto, Jens C.; Coelho-Rato, Leila S.; Jungarå, Cecilia; Bengs, Sara H.; Roininen, Jannica; Eriksson, John E.; Sistonen, Lea; Henriksson, Eva
Publisher: John Wiley & Sons
Publication year: 2023
Journal: Journal of Extracellular Biology
Journal name in source: Journal of extracellular biology
Journal acronym: J Extracell Biol
Article number: e124
Volume: 2
Issue: 12
ISSN: 2768-2811
eISSN: 2768-2811
DOI: https://doi.org/10.1002/jex2.124
Web address : https://doi.org/10.1002/jex2.124
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/457067908
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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Funding information in the publication:
This project was funded by Åbo Akademi University (JCL, LS, EH), Academy of Finland (LS), the Medical Research Foundation Liv och Hälsa (LS, EH), Sigrid Jusélius Foundation (LS), Cancer Society of Finland (LS), Otto A. Malm Foundation (EH), Magnus Ehrnrooth Foundation (LS, EH), Swedish Cultural Foundation (JCL, EH), K. Albin Johansson Foundation (JCL, EH), Victoriastiftelsen (JCL), and the Ella and Georg Ehrnrooth Foundation (JCL, EH).
