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Integrins are enriched on aberrantly fucosylated tumour‐derived urinary extracellular vesicles
Journal of Extracellular Biology, Volume: 1, Issue: 10
Swansea University Author: Jason Webber
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DOI (Published version): 10.1002/jex2.64
Urinary extracellular vesicles (uEVs) are enriched with glycosylated proteins which have been extensively studied as putative biomarkers of urological cancers. Here, we characterized the glycosylation and integrin profile of EVs derived from urological cancer cell lines. We used fluorescent europium...
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Urinary extracellular vesicles (uEVs) are enriched with glycosylated proteins which have been extensively studied as putative biomarkers of urological cancers. Here, we characterized the glycosylation and integrin profile of EVs derived from urological cancer cell lines. We used fluorescent europium-doped nanoparticles coated with lectins and antibodies to identify a biomarker combination consisting of integrin subunit alpha 3 (ITGA3) and fucose. In addition, we used the same cancer cell line-derived EVs as analytical standards to assess the sensitivity of the ITGA3-UEA assay. The clinical performance of the ITGA3-UEA assay was analysed using urine samples of various urological pathologies including diagnostically challenging benign prostatic hyperplasia (BPH), prostate cancer (PCa) and bladder cancer (BlCa). The assay can significantly discriminate BlCa from all other patient groups: PCa (9.2-fold; p = 0.00038), BPH (5.5-fold; p = 0.004) and healthy individuals (and 23-fold; p = 0.0001). Our results demonstrate that aberrantly fucosylated uEVs and integrin ITGA3 can be detected with fucose-specific lectin UEA in a simple bioaffinity assay for the detection of BlCa directly from unprocessed urin
Bladder cancer, Extracellular vesicle, Glycosylation, Immunoassay, Integrin, Lectin, Nanoparticle, Prostatecancer, Prostate cancer
Faculty of Medicine, Health and Life Sciences
This work is supported by DPMLS-University of Turku graduate school (University of Turku), Academy of Finland (grant no.:309950/2017), Nanolec project funded by Jane and Aatos Erkko Foundation, MSCA-ITN project proEVLifeCycle (EuropeanUnion’s Horizon 2020 research and innovation programme under grant agreement No 860303) and by InFLAMES FlagshipProgramme of the Academy of Finland (decision number: 337530).