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

• Published in: Cell communication and signaling Vol. 18; no. 1; p. 158
• Main Authors: Altei, Wanessa F, Pachane, Bianca C, Dos Santos, Patty K, Ribeiro, Lígia N M, Sung, Bong Hwan, Weaver, Alissa M, Selistre-de-Araújo, Heloisa S
• Format: Journal Article
• Language: English
• Published: England BioMed Central 25.09.2020; BMC
• Subjects: Adhesion; Breast - pathology; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; CD63 antigen; Cell Adhesion; Cell adhesion & migration; Cell culture; Cell interactions; Cell Line, Tumor; Cell migration; Cell signaling; Centrifugation; Collagen; Drug resistance; Epithelial cells; Epithelial Cells - metabolism; Experiments; Extracellular matrix; Extracellular Matrix - metabolism; Extracellular Matrix Proteins - metabolism; Extracellular vesicles; Extracellular Vesicles - metabolism; Extracellular Vesicles - ultrastructure; Female; Fibronectin; Green Fluorescent Proteins - metabolism; Humans; Integrin alphaVbeta3 - metabolism; Integrins; Metastases; Metastasis; Microscopy; Models, Biological; Peptides; Protein Binding; Proteins; Small extracellular vesicles; Tissue culture; Uptake; αvβ3 integrin; United States > US; Breast cancer; Small extracellular vesicles; αvβ3 integrin; Adhesion; Uptake
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/s12964-020-00630-w

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