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Title: The role of stress-derived vesicles in the bystander effect and cancer related cachexia
Author: Bewicke-Copley, Findlay R.
ISNI:       0000 0004 7971 7441
Awarding Body: Oxford Brookes University
Current Institution: Oxford Brookes University
Date of Award: 2018
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Extracellular vesicles are small, lipid bound structures that are involved in intercellular signalling. They are known to be involved in numerous processes within the body, including in disease. One interesting function of EVs appears to be the induction of the bystander effect. The bystander effect refers to the non-targeted effects of stress, whereby stressed cells induce damage in neighbouring cells. EVs released from cells following irradiation have previously been shown to induce the bystander effect. EVs have also been implicated in the induction of cancer-cachexia, a muscle wasting disease. This disease is common in patients with cancer and is often linked to poor prognosis. In this project the ability of EVs released from heat shocked cells to induce bystander effects has been assessed. EVs released from cancer cells following 45°C treatment induced the bystander effect and the bystander cells were shown to be more resistant to subsequent stress treatment. EVs retained this functionality for up to two weeks when stored at -80°C. EVs released following short, 70°C treatment were also able to induce bystander effects. The ability of EVs from both stressed (cisplatin) and unstressed cancer cells to induce cachexia was also examined. Cancer EVs were able to reduce differentiation in vitro, but no effects were observed when these EVs were injected into mice. The proteome of these EVs and their parent cells was also identified via liquid chromatography-mass spectrometry and pathway analysis was carried out on these proteins. These data suggest possible roles for EVs in cell-cell communication during stress and disease, with EVs being able to induce bystander effects and alter muscle development in vitro.
Supervisor: Pink, Ryan ; Carter, David Sponsor: Oxford Brookes University ; Cancer and Polio Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral