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dc.contributor.advisorDwyer, Róisín M.
dc.contributor.authorJoyce, Doireann
dc.date.accessioned2017-05-11T09:24:34Z
dc.date.available2017-05-11T09:24:34Z
dc.date.issued2016-06-15
dc.identifier.urihttp://hdl.handle.net/10379/6510
dc.description.abstractBreast cancer is a heterogeneous group of diseases survival from which depends on stage at diagnosis. The development of blood-based biomarkers which may facilitate earlier detection and possibly subtype delineation remains the focus of international research efforts. Exosomes are membrane-derived vesicles that are actively secreted by cells and have been shown to play a role in intercellular communication in the primary breast tumour microenvironment. Exosomes contain genetic material including microRNAs (miRNA), which have the potential to function as circulating biomarkers for breast cancer. In this work, a retrospective cohort study comparing outcomes from Triple-negative and Non-Triple-negative breast cancer was used to demonstrate the inferior prognosis that is associated with the triple-negative phenotype. Exosomes were isolated from breast cancer cell lines and using Transmission Electron Microscopy and Western Blot Analysis were shown to have the characteristic shape, size (30-120nm) and associated protein (CD63). Transfer of exosomes to recipient cells, which was visualized using confocal microscopy, was shown to be capable of stimulating angiogenesis. Cell-secreted exosomal miRNAs were profiled and potentially interesting targets were investigated in matched whole blood and serum exosomal samples of patients with breast cancer and healthy controls. MiR-451a was found to be up-regulated in serum exosomes of patients with breast cancer. An in vivo model of breast cancer was also established to identify serum exosomal miRNAs that may be indicative of breast cancer. MiR-223 was identified as being potentially valuable for subtype discrimination in breast cancer. This work highlighted the need for an exosome-specific marker which would allow accurate isolation, characterisation and quantification of these microvesicles. Furthermore, the requirement for robust endogenous controls for use in serum exosomal work in addition to the importance of reproducible data normalisation was demonstrated. This exciting field offers huge potential and the clinical applicability of serum exosomal miRNAs will be investigated going forward.en_IE
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/
dc.subjectBreast canceren_IE
dc.subjectExosomesen_IE
dc.subjectBiomarkeren_IE
dc.subjectCirculating biomarkeren_IE
dc.subjectSurgeryen_IE
dc.subjectMedicineen_IE
dc.titleExosome-encapsulated microRNAs as circulating biomarkers for breast canceren_IE
dc.typeThesisen_IE
dc.local.noteExosomes are small packages that are released from cells into the bloodstream. They contain a variety of molecules, some of which may be used to identify the presence of cancer. This work aimed to determine if exosomes could be used to detect breast cancer and to monitor response to treatment.en_IE
dc.local.finalYesen_IE
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Ireland