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dc.contributor.authorBjørnetrø, Tonje
dc.contributor.authorRedalen, Kathrine
dc.contributor.authorMeltzer, Sebastian
dc.contributor.authorThusyanthan, Nirujah Sivarajah
dc.contributor.authorSamiappan, Rampradeep
dc.contributor.authorJegershöld, Caroline
dc.contributor.authorHandeland, Karianne Risberg
dc.contributor.authorRee, Anne Hansen
dc.date.accessioned2019-09-25T07:20:38Z
dc.date.available2019-09-25T07:20:38Z
dc.date.created2019-03-07T12:21:58Z
dc.date.issued2019
dc.identifier.citationJournal of Extracellular Vesicles. 2019, 8:1567219 (1), 1-13.nb_NO
dc.identifier.issn2001-3078
dc.identifier.urihttp://hdl.handle.net/11250/2618622
dc.description.abstractTumour hypoxia contributes to poor treatment outcome in locally advanced rectal cancer (LARC) and circulating extracellular vesicles (EVs) as potential biomarkers of tumour hypoxia and adverse prognosis have not been fully explored. We examined EV miRNAs from hypoxic colorectal cancer cell lines as template for relevant miRNAs in LARC patients participating in a prospective biomarker study (NCT01816607). Five cell lines were cultured under normoxia (21% O2) or hypoxia (0.2% O2) for 24 h, and exosomes were isolated by differential ultracentrifugation. Using a commercial kit, exosomes were precipitated from 24 patient plasma samples collected at the time of diagnosis. Exosome size distribution and protein cargo were determined by cryo-electron microscopy, nanoparticle tracking analysis, immunoblotting and flow cytometry. The vesicles harboured strong cell line-specific miRNA profiles with 35 unique miRNAs differentially expressed between hypoxic and normoxic cells. Six of these miRNAs were considered candidate-circulating markers of tumour hypoxia in the patients based on the frequency or magnitude of variance in hypoxic versus normoxic cell line experiments and prevalence in patient plasma. Of these, low plasma levels of exosomal miR-486-5p and miR-181a-5p were associated with organ-invasive primary tumour (p = 0.029) and lymph node metastases (p = 0.024), respectively, both attributes of adverse LARC prognosis. In line with this, the plasma level of exosomal miR-30d-5p was elevated in patients who experienced metastatic progression (p = 0.036). Our strategy confirmed that EVs from colorectal cancer cell lines were exosomes containing the oxygen-sensitive miRNAs 486-5p, 181a-5p and 30d-5p, which were retrieved as circulating markers of high-risk LARC.nb_NO
dc.language.isoengnb_NO
dc.publisherTaylor & Francisnb_NO
dc.rightsNavngivelse-Ikkekommersiell 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/deed.no*
dc.titleAn experimental strategy unveiling exosomal microRNAs 486-5p, 181a-5p and 30d-5p from hypoxic tumour cells as circulating indicators of high-risk rectal cancernb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.pagenumber1-13nb_NO
dc.source.volume8:1567219nb_NO
dc.source.journalJournal of Extracellular Vesiclesnb_NO
dc.source.issue1nb_NO
dc.identifier.doi10.1080/20013078.2019.1567219
dc.identifier.cristin1682889
dc.description.localcode© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.nb_NO
cristin.unitcode194,66,20,0
cristin.unitnameInstitutt for fysikk
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


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Navngivelse-Ikkekommersiell 4.0 Internasjonal
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