Blood flow diverts extracellular vesicles from endothelial degradative compartments to promote angiogenesis

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Abstract: Extracellular vesicles released by tumors (tEVs) disseminate via circulatory networks and promote microenvironmental changes in distant organs favoring metastatic seeding. Despite their abundance in the bloodstream, how hemodynamics affect the function of circulating tEVs remains unsolved. We demonstrated that efficient uptake of tEVs occurs in venous endothelial cells that are subjected to hemodynamics. Low flow regimes observed in veins partially reroute internalized tEVs toward non‐acidic and non‐degradative Rab14‐positive endosomes, at the expense of lysosomes, suggesting that endothelial mechanosensing diverts tEVs from degradation. Subsequently, tEVs promote the expression of pro‐angiogenic transcription factors in low flow‐stimulated endothelial cells and favor vessel sprouting in zebrafish. Altogether, we demonstrate that low flow regimes potentiate the pro‐tumoral function of circulating tEVs by promoting their uptake and rerouting their trafficking. We propose that tEVs contribute to pre‐metastatic niche formation by exploiting endothelial mechanosensing in specific vascular regions with permissive hemodynamics.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Blood flow diverts extracellular vesicles from endothelial degradative compartments to promote angiogenesis ; day:16 ; month:11 ; year:2023 ; extent:22
EMBO reports / European Molecular Biology Organization ; (16.11.2023) (gesamt 22)

Urheber
Mary, Benjamin
Asokan, Nandini
Jerabkova‐Roda, Katerina
Larnicol, Annabel
Busnelli, Ignacio
Stemmelen, Tristan
Pichot, Angélique
Molitor, Anne
Carapito, Raphaël
Lefebvre, Olivier
Goetz, Jacky G.
Hyenne, Vincent

DOI
10.15252/embr.202357042
URN
urn:nbn:de:101:1-2023111714015023461025
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:22 MESZ

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Beteiligte

  • Mary, Benjamin
  • Asokan, Nandini
  • Jerabkova‐Roda, Katerina
  • Larnicol, Annabel
  • Busnelli, Ignacio
  • Stemmelen, Tristan
  • Pichot, Angélique
  • Molitor, Anne
  • Carapito, Raphaël
  • Lefebvre, Olivier
  • Goetz, Jacky G.
  • Hyenne, Vincent

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