Journal
JOURNAL OF EXTRACELLULAR VESICLES
Volume 10, Issue 2, Pages -Publisher
WILEY
DOI: 10.1002/jev2.12039
Keywords
drug design; exosomes; inhibitors; PDZ; syndecan; Syntenin
Categories
Funding
- Concerted Actions Program of the KU Leuven [GOA/12/016]
- National Research Agency (ANR, Investissements d'Avenir, AMIDEX project) [ANR-11-IDEX-0001-02]
- Fund for Scientific Research-Flanders (Fonds Wetenschappelijk Onderzoek-Vlaanderen Grants) [G.0846.15, G0C5718N]
- Institut National du Cancer (INCa) [2013-105]
- Belgian Foundation against cancer (STK) [FA/2014/294]
- French National Research Agency [ANR-18-CE13-0017]
- French Infrastructure for Integrated Structural Biology (FRISBI) [ANR-10-INSB-05-01]
- European Union [747025]
- La Ligue French Foundation for Cancer Research
- ARC French Foundation for Cancer Research
- Agence Nationale de la Recherche (ANR) [ANR-18-CE13-0017] Funding Source: Agence Nationale de la Recherche (ANR)
- Marie Curie Actions (MSCA) [747025] Funding Source: Marie Curie Actions (MSCA)
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Exosomes support cell-to-cell communication in physiology and disease, including cancer. We currently lack tools, such as small chemicals, capable of modifying exosome composition and activity in a specific manner. Building on our previous understanding of how syntenin, and its PDZ partner syndecan (SDC), impact on exosome composition we optimized a small chemical compound targeting the PDZ2 domain of syntenin. In vitro , in tests on MCF-7 breast carcinoma cells, this compound is non-toxic and impairs cell proliferation, migration and primary sphere formation. It does not affect the size or the number of secreted particles, yet it decreases the amounts of exosomal syntenin, ALIX and SDC4 while leaving other exosomal markers unaffected. Interestingly, it also blocks the sorting of EpCAM, a bona fide target used for carcinoma exosome immunocapture. Our study highlights the first characterization of a small pharmacological inhibitor of the syntenin-exosomal pathway, of potential interest for exosome research and oncology.
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