A microfluidic chip enables isolation of exosomes and establishment of their protein profiles and associated signaling pathways in ovarian cancer

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dc.contributor.author Dorayappan, KDP en
dc.contributor.author Gardner, ML en
dc.contributor.author Hisey, Colin en
dc.contributor.author Zingarelli, RA en
dc.contributor.author Smith, BQ en
dc.contributor.author Lightfoot, MDS en
dc.contributor.author Gogna, R en
dc.contributor.author Flannery, MM en
dc.contributor.author Hays, J en
dc.contributor.author Hansford, DJ en
dc.contributor.author Freitas, MA en
dc.contributor.author Yu, L en
dc.contributor.author Cohn, DE en
dc.contributor.author Selvendiran, K en
dc.date.accessioned 2019-09-19T03:52:03Z en
dc.date.issued 2019-07 en
dc.identifier.citation Cancer Research 79(13):3503-3513 Jul 2019 en
dc.identifier.issn 0008-5472 en
dc.identifier.uri http://hdl.handle.net/2292/47818 en
dc.description.abstract Due to limits on specificity and purity to allow for in-depth protein profiling, a standardized method for exosome isolation has yet to be established. In this study, we describe a novel, in-house microfluidic-based device to isolate exosomes from culture media and patient samples. This technology overcomes contamination issues because sample separation is based on the expression of highly specific surface markers CD63 and EpCAM. Top exosome proteins were identified based on their fold change and statistical significance between groups. Mass spectrometry revealed over 25 exosome proteins that are differentially expressed in high-grade serous ovarian cancer (HGSOC) cell lines compared to normal cells - ovarian surface epithelia cells (OSE) and fallopian tube secretory epithelial cells (FTSEC). Ingenuity Pathway Analysis identified STAT3 and HGF as top regulator proteins. We further validated exosome proteins of interest (pSTAT3, HGF, and IL-6) in HGSOC samples of origin-based cell lines (OVCAR-8, FTSEC) and in early stage HGSOC patient serum exosome samples using LC-MS/MS and Proximity Extension Assay (PEA). Our microfluidic device will allow us to make new discoveries for exosome-based biomarkers for the early detection of HGSOC and contribute to the development of new targeted therapies based on signaling pathways that are unique to HGSOC, both of which could improve the outcome for women with HGSOC. en
dc.publisher American Association for Cancer Research en
dc.relation.ispartofseries Cancer Research en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri https://aacrjournals.org/content/authors/copyright-permissions-and-access en
dc.title A microfluidic chip enables isolation of exosomes and establishment of their protein profiles and associated signaling pathways in ovarian cancer en
dc.type Journal Article en
dc.identifier.doi 10.1158/0008-5472.CAN-18-3538 en
pubs.issue 13 en
pubs.begin-page 3503 en
pubs.volume 79 en
dc.rights.holder Copyright: American Association for Cancer Research en
pubs.end-page 3513 en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype Article en
pubs.elements-id 776146 en
pubs.org-id Medical and Health Sciences en
pubs.org-id School of Medicine en
pubs.org-id Obstetrics and Gynaecology en
pubs.record-created-at-source-date 2019-07-08 en
pubs.online-publication-date 2019-05-16 en


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