Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.758383
Title: Tumour-stromal crosstalk in metastatic lymph nodes of oral squamous cell carcinoma
Author: Pilborough, Alice Elizabeth
ISNI:       0000 0004 7431 1565
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2018
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Abstract:
The prognosis of patients with oral squamous cell carcinoma (OSCC) worsens dramatically when tumours metastasise to neck lymph nodes, particularly when they spread beyond the node capsule (extracapsular spread, ECS). Although the importance of the tumour microenvironment has been well established in OSCC, it is poorly understood in the context of ECS and lymph node metastases. This work aimed to examine the lymph node tumour microenvironment in ECS and to investigate the mechanisms of tumour-stromal crosstalk, which may drive lymph node tumour development. Stromal and epithelial-mesenchymal transition (EMT) markers in paired primary and lymph node tumours with and without ECS were compared by IHC. It was found that the stroma of ECS-positive lymph nodes and their matched primary tumours have a higher proportion of aSMA-positive myofibroblasts and that microvascular vessel density is also elevated in ECS-positive nodes. Key stromal cell types including myofibroblasts, senescent fibroblasts, cancer-associated fibroblasts (CAF), vascular and lymphatic endothelial cells were co-cultured with oral cancer cell lines (OCCL), including those derived from lymph node metastases. EMT marker expression was detected in metastatic OCCL, which also showed significantly higher migration capacity, but more work is needed to determine the impact of fibroblasts on these processes. Both primary and metastases-derived OCCL induced tubule formation in lymphatic endothelial cells. OCCL, particularly those derived from lymph node metastases, and were also able to induce IL-6 and CCL2 secretion in normal oral fibroblasts and exposure of endothelial cells to OCCL and fibroblast conditioned media also resulted in a significant increase in expression of the inflammatory mediator IL-6. The findings of this thesis describe novel data relating to the role of the tumour microenvironment in lymph node metastases and ECS. Increased understanding of this process will aid the development of new biomarkers and treatment options for patients with advanced OSCC.
Supervisor: Khurram, Syed Ali ; Lambert, Daniel W. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.758383  DOI: Not available
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