Increasing evidence indicates that breast cancer stem-like cells (CSCs) are responsible for tumour initiation, maintenance, metastases and disease recurrence. HER2 over-expression is reported to increase the proportion of breast CSCs, and this may, at least in part, provide an explanation for the poor prognosis of these tumours. Trastuzumab has improved the survival of HER2 positive patients and this is postulated to be due to inhibition of HER2 positive CSC activity. However, in most cases this is insufficient to eradicate the disease, indicating that other factors are important in driving the activity of HER2 positive breast CSCs. Interleukin-8 (IL-8) is upregulated in breast cancer compared to normal breast tissue and is associated with poor prognosis. Recent breast cancer cell line studies indicate that IL-8 via its cognate receptors, CXCR1 and CXCR2, is important in regulating breast CSC activity. The aims of this thesis were to investigate the role of CXCR1/2 in the regulation of breast CSC activity in patient-derived breast cancers and determine the potential benefit of combining CXCR1/2 inhibition with HER2-targeted therapy. The mammosphere assay was used to assess breast CSC activity and self-renewal. Metastatic fluid IL-8 level correlated directly with mammosphere formation when tumour cells from these fluid were cultured ex vivo (r = 0.652; P
Date of Award | 1 Aug 2013 |
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Original language | English |
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Awarding Institution | - The University of Manchester
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Supervisor | Nigel Bundred (Supervisor) & Robert Clarke (Supervisor) |
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- Breast Cancer, Stem Cell, HER2, IL-8, CXCR1, CXCR2
The Role of CXCR1/2 and HER2 Signalling in the Regulation of Stem Cell Activity in Breast Cancer
Singh, J. (Author). 1 Aug 2013
Student thesis: Doctor of Medicine