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

Autor: Wanessa F. Altei, Bianca C. Pachane, Patty K. dos Santos, Lígia N. M. Ribeiro, Bong Hwan Sung, Alissa M. Weaver, Heloisa S. Selistre-de-Araújo
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cell Communication and Signaling, Vol 18, Iss 1, Pp 1-15 (2020)
Druh dokumentu: article
ISSN: 1478-811X
DOI: 10.1186/s12964-020-00630-w
Popis: Abstract 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 Graphical abstract
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