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dc.contributor.authorO’Brien, K. P.
dc.contributor.authorKhan, S.
dc.contributor.authorGilligan, K. E.
dc.contributor.authorZafar, H.
dc.contributor.authorLalor, P.
dc.contributor.authorGlynn, C.
dc.contributor.authorO’Flatharta, C.
dc.contributor.authorIngoldsby, H.
dc.contributor.authorDockery, P.
dc.contributor.authorDe Bhulbh, A.
dc.contributor.authorSchweber, J. R.
dc.contributor.authorSt John, K.
dc.contributor.authorLeahy, M.
dc.contributor.authorMurphy, J. M.
dc.contributor.authorGallagher, W. M.
dc.contributor.authorO’Brien, T.
dc.contributor.authorKerin, Michael J.
dc.contributor.authorDwyer, Róisín M.
dc.date.accessioned2019-09-03T13:21:59Z
dc.date.available2019-09-03T13:21:59Z
dc.date.issued2018-01-25
dc.identifier.citationO’Brien, K. P., Khan, S., Gilligan, K. E., Zafar, H., Lalor, P., Glynn, C., , O’Flatharta, C., Ingoldsby, H., Dockery, P. De Bhulbh, A., Schweber, J. R., St John, K., Leahy, M., Murphy, J. M., Gallagher, W. M., O’Brien, T., Kerin, M. J., Dwyer, R. M., Dwyer, R. M. (2018). Employing mesenchymal stem cells to support tumor-targeted delivery of extracellular vesicle (EV)-encapsulated microRNA-379. Oncogene, 37(16), 2137-2149. doi: 10.1038/s41388-017-0116-9en_IE
dc.identifier.issn1476-5594
dc.identifier.urihttp://hdl.handle.net/10379/15377
dc.description.abstractAdult Mesenchymal Stem Cells (MSCs) have a well-established tumor-homing capacity, highlighting potential as tumor-targeted delivery vehicles. MSCs secrete extracellular vesicle (EV)-encapsulated microRNAs, which play a role in intercellular communication. The aim of this study was to characterize a potential tumor suppressor microRNA, miR-379, and engineer MSCs to secrete EVs enriched with miR-379 for in vivo therapy of breast cancer. miR-379 expression was significantly reduced in lymph node metastases compared to primary tumor tissue from the same patients. A significant reduction in the rate of tumor formation and growth in vivo was observed in T47D breast cancer cells stably expressing miR-379. In more aggressive HER2-amplified HCC-1954 cells, HCC-379 and HCC-NTC tumor growth rate in vivo was similar, but increased tumor necrosis was observed in HCC-379 tumors. In response to elevated miR-379, COX-2 mRNA and protein was also significantly reduced in vitro and in vivo. MSCs were successfully engineered to secrete EVs enriched with miR-379, with the majority found to be of the appropriate size and morphology of exosomal EVs. Administration of MSC-379 or MSC-NTC cells, or EVs derived from either cell population, resulted in no adverse effects in vivo. While MSC-379 cells did not impact tumor growth, systemic administration of cell-free EVs enriched with miR-379 was demonstrated to have a therapeutic effect. The data presented support miR-379 as a potent tumor suppressor in breast cancer, mediated in part through regulation of COX-2. Exploiting the tumor-homing capacity of MSCs while engineering the cells to secrete EVs enriched with miR-379 holds exciting potential as an innovative therapy for metastatic breast cancer.en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherSpringer Natureen_IE
dc.relation.ispartofOncogeneen
dc.subjectBREAST-CANCERen_IE
dc.subjectCYCLOOXYGENASE-2 EXPRESSIONen_IE
dc.subjectPANCREATIC-CANCERen_IE
dc.subjectSTROMAL CELLSen_IE
dc.subjectEXOSOMESen_IE
dc.subjectMETASTASISen_IE
dc.subjectTHERAPYen_IE
dc.subjectMECHANISMen_IE
dc.subjectAPOPTOSISen_IE
dc.subjectMIR-379en_IE
dc.titleEmploying mesenchymal stem cells to support tumor-targeted delivery of extracellular vesicle (EV)-encapsulated microRNA-379en_IE
dc.typeArticleen_IE
dc.date.updated2019-08-16T10:11:23Z
dc.identifier.doi10.1038/s41388-017-0116-9
dc.local.publishedsourcehttps://dx.doi.org/10.1038/s41388-017-0116-9en_IE
dc.description.peer-reviewedpeer-reviewed
dc.internal.rssid14285569
dc.local.contactRóisín Dwyer, Surgery, Nui Galway. 3008 Email: roisin.dwyer@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionACCEPTED
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