Exosomes are specialized vehicles to induce fibronectin assembly
Year: 2025
Type: preprint
Abstract: Fibronectin is a key stromal matrix molecule whose assembly into fibrils is thought to require cells. In contrast, we find that small exosome-type extracellular vesicles (EVs) are critical initiators of fibronectin assembly. Fibroblasts engineered to be deficient in exosome secretion showed greatly reduced assembly of fibronectin and other stromal matrix molecules in 2D, 3D, and in vivo environments, and led to reduced tumor growth and lung metastasis by breast cancer cells. Furthermore, transgenic mice with defects in exosome secretion had greatly reduced lung fibrosis after treatment with bleomycin. In a direct test of exosome function, we find that the addition of purified small EVs to purified soluble fibronectin in a cell-free system is sufficient to induce fibronectin assembly. The EV-induced fibronectin assembly requires the presence of fibronectin-binding integrins and Syndecan-1 in the EVs. We propose a new model in which secreted exosomes directly drive stromal matrix assembly and tissue fibrosis.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Vanderbilt Mouse Metabolic Phenotyping Center, Exosome Secretion in Tumor Aggressiveness, Conventional 200 keV Transmission Electron Microscope, Exosome function in stromal matrix assembly, Molecular and Cellular Basis for Digestive Diseases, Exosome secretion in breast cancer progression, Cancer Center Support Grant, Regulation of extracellular vesicle biogenesis through cell adhesion, Vanderbilt Diabetes Research Center, Core Grant in Vision Research, Exosomes in HNSCC Progression
OpenAlex ID: W4411593256