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Integrins are enriched on aberrantly fucosylated tumour‐derived urinary extracellular vesicles

Md. Khirul Islam, Bert Dhondt, Parvez Syed, Misba Khan, Kamlesh Gidwani, Jason Webber Orcid Logo, An Hendrix, Guido Jenster, Tarja Lamminen, Peter J. Boström, Kim Pettersson, Urpo Lamminmäki, Janne Leivo

Journal of Extracellular Biology, Volume: 1, Issue: 10

Swansea University Author: Jason Webber Orcid Logo

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DOI (Published version): 10.1002/jex2.64

Abstract

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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Published in: Journal of Extracellular Biology
ISSN: 2768-2811 2768-2811
Published: Wiley 2022
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URI: https://cronfa.swan.ac.uk/Record/cronfa61589
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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). 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spelling v2 61589 2022-10-19 Integrins are enriched on aberrantly fucosylated tumour‐derived urinary extracellular vesicles 25d1a26f9b8bb556bd9412080e40351d 0000-0003-4772-3014 Jason Webber Jason Webber true false 2022-10-19 BMS 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 Journal Article Journal of Extracellular Biology 1 10 Wiley 2768-2811 2768-2811 Bladder cancer, Extracellular vesicle, Glycosylation, Immunoassay, Integrin, Lectin, Nanoparticle, Prostatecancer, Prostate cancer 10 10 2022 2022-10-10 10.1002/jex2.64 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 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). 2023-09-13T16:57:56.9370166 2022-10-19T10:57:03.6952771 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Md. Khirul Islam 1 Bert Dhondt 2 Parvez Syed 3 Misba Khan 4 Kamlesh Gidwani 5 Jason Webber 0000-0003-4772-3014 6 An Hendrix 7 Guido Jenster 8 Tarja Lamminen 9 Peter J. Boström 10 Kim Pettersson 11 Urpo Lamminmäki 12 Janne Leivo 13 61589__25497__60cac1edfe04402ea64abf819079ea8e.pdf 61589_VoR.pdf 2022-10-19T11:03:00.5874510 Output 2698902 application/pdf Version of Record true © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License true eng http://creativecommons.org/licenses/by-nc/4.0/
title Integrins are enriched on aberrantly fucosylated tumour‐derived urinary extracellular vesicles
spellingShingle Integrins are enriched on aberrantly fucosylated tumour‐derived urinary extracellular vesicles
Jason Webber
title_short Integrins are enriched on aberrantly fucosylated tumour‐derived urinary extracellular vesicles
title_full Integrins are enriched on aberrantly fucosylated tumour‐derived urinary extracellular vesicles
title_fullStr Integrins are enriched on aberrantly fucosylated tumour‐derived urinary extracellular vesicles
title_full_unstemmed Integrins are enriched on aberrantly fucosylated tumour‐derived urinary extracellular vesicles
title_sort Integrins are enriched on aberrantly fucosylated tumour‐derived urinary extracellular vesicles
author_id_str_mv 25d1a26f9b8bb556bd9412080e40351d
author_id_fullname_str_mv 25d1a26f9b8bb556bd9412080e40351d_***_Jason Webber
author Jason Webber
author2 Md. Khirul Islam
Bert Dhondt
Parvez Syed
Misba Khan
Kamlesh Gidwani
Jason Webber
An Hendrix
Guido Jenster
Tarja Lamminen
Peter J. Boström
Kim Pettersson
Urpo Lamminmäki
Janne Leivo
format Journal article
container_title Journal of Extracellular Biology
container_volume 1
container_issue 10
publishDate 2022
institution Swansea University
issn 2768-2811
2768-2811
doi_str_mv 10.1002/jex2.64
publisher Wiley
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description 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
published_date 2022-10-10T16:57:59Z
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