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Inhibition of αvβ3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles
- Source :
- Cell Communication and Signaling : CCS, Cell Communication and Signaling, Vol 18, Iss 1, Pp 1-15 (2020)
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
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. Graphical abstract
- Subjects :
- Green Fluorescent Proteins
Integrin
lcsh:Medicine
Uptake
Breast Neoplasms
Small extracellular vesicles
Models, Biological
Biochemistry
Extracellular matrix
Extracellular Vesicles
03 medical and health sciences
Tissue culture
Breast cancer
0302 clinical medicine
Cell Line, Tumor
Cell Adhesion
Disintegrin
Humans
Breast
lcsh:QH573-671
Receptor
Molecular Biology
030304 developmental biology
Integrin binding
Extracellular Matrix Proteins
0303 health sciences
biology
lcsh:Cytology
Chemistry
Research
αvβ3 integrin
lcsh:R
Epithelial Cells
Cell Biology
Adhesion
Integrin alphaVbeta3
Extracellular Matrix
Cell biology
030220 oncology & carcinogenesis
Cancer cell
biology.protein
Female
Protein Binding
Subjects
Details
- ISSN :
- 1478811X
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Cell Communication and Signaling
- Accession number :
- edsair.doi.dedup.....2719e3463f32eb3a71292b45677ff337