Inhibition of αvβ3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles

Cell Commun Signal. 2020 Sep 25;18(1):158. doi: 10.1186/s12964-020-00630-w.


Background: Extracellular vesicles (EVs) are lipid-bound particles that are naturally released from cells and mediate cell-cell communication. Integrin adhesion receptors are enriched in small EVs (SEVs) and SEV-carried integrins have been shown to promote cancer cell migration and to mediate organ-specific metastasis; however, how integrins mediate these effects is not entirely clear and could represent a combination of EV binding to extracellular matrix and cells.

Methods: To probe integrin role in EVs binding and uptake, we employed a disintegrin inhibitor (DisBa-01) of integrin binding with specificity for αvβ3 integrin. EVs were purified from MDA-MB-231 cells conditioned media by serial centrifugation method. Isolated EVs were characterized by different techniques and further employed in adhesion, uptake and co-culture experiments.

Results: We find that SEVs secreted from MDA-MB-231 breast cancer cells carry αvβ3 integrin and bind directly to fibronectin-coated plates, which is inhibited by DisBa-01. SEV coating on tissue culture plates also induces adhesion of MDA-MB-231 cells, which is inhibited by DisBa-01 treatment. Analysis of EV uptake and interchange between cells reveals that the amount of CD63-positive EVs delivered from malignant MDA-MB-231 breast cells to non-malignant MCF10A breast epithelial cells is reduced by DisBa-01 treatment. Inhibition of αvβ3 integrin decreases CD63 expression in cancer cells suggesting an effect on SEV content.

Conclusion: In summary, our findings demonstrate for the first time a key role of αvβ3 integrin in cell-cell communication through SEVs. Video Abstract.

Keywords: Adhesion; Breast cancer; Small extracellular vesicles; Uptake; αvβ3 integrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast / pathology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Adhesion
  • Cell Line, Tumor
  • Epithelial Cells / metabolism
  • Extracellular Matrix / metabolism
  • Extracellular Matrix Proteins / metabolism
  • Extracellular Vesicles / metabolism*
  • Extracellular Vesicles / ultrastructure
  • Female
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Integrin alphaVbeta3 / metabolism*
  • Models, Biological
  • Protein Binding


  • Extracellular Matrix Proteins
  • Integrin alphaVbeta3
  • Green Fluorescent Proteins