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

Cell Communication and Signaling

Bianca C. Pachane¹  Patty K. dos Santos¹  Wanessa F. Altei¹  Heloisa S. Selistre-de-Araújo¹  Lígia N. M. Ribeiro²  Bong Hwan Sung³  Alissa M. Weaver⁴ 

[1] Biochemistry and Molecular Biology Laboratory, Department of Physiological Sciences, Federal University of São Carlos, São Carlos, Brazil;Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas-UNICAMP, Campinas, São Paulo, Brazil;Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, USA;Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, USA;Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, USA;

关键词: Small extracellular vesicles;    αvβ3 integrin;    Adhesion;    Uptake;    Breast cancer;   

DOI  :  10.1186/s12964-020-00630-w

来源: Springer

【 摘 要 】

BackgroundExtracellular 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.MethodsTo 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.ResultsWe 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.ConclusionIn summary, our findings demonstrate for the first time a key role of αvβ3 integrin in cell-cell communication through SEVs.6Ak9CS6CfK5Ku3JS4e63coVideo AbstractGraphical abstract

【 授权许可】

CC BY