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Title: Physiological studies of thrombospondin
Author: Pratt, David Andrew
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1991
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Thrombospondin (TSP), a glycoprotein of wide cellular distribution, exhibits several activities important in platelet aggregation, haemostasis and cell adhesion. The aim of this project was to investigate the production and role of TSP in human tissues and fluids; particularly its source in the breast and relation to malignant disease. Most circulating TSP was contained within platelet α-granules and released upon activation of these cells. Infused TSP appeared to be rapidly bound, whilst its clearance from the circulation was relatively slow. Extra-platelet sources contributed substantially to basal plasma levels; platelet-associated TSP may therefore be a better indicator of platelet activation than plasma concentration. TSP concentration in breast cyst fluids varied according to cyst type and correlated inversely with epidermal growth factor. TSP was present in milk at high levels compared with plasma and its pattern of secretion resembled that of IgA; it may be that white cells which infiltrate the mammary gland are a major source of TSP in breast secretions. Very high levels of TSP were found in malignant breast tissue compared with non-malignant breast and were associated with the centre of the tumour mass. Positive correlation between TSP and von Willebrand factor suggested that endothelium contributes to the high levels of both proteins in malignant breast, whereas lack of correlation between TSP and tissue plasminogen activator argued against epithelium being the source of TSP in breast cancer. In conclusion, the results presented in this thesis support current knowledge of TSP as an adhesive glycoprotein of platelets, vessel walls and connective tissues. Novel studies in the breast have revealed a marked association of TSP with cancerous tissue and some cyst fluids, which could be due to production by vascular endothelium and certain white blood cells. Whilst the role of TSP in the breast remains to be defined, its relation to disease states may be of particular physiological significance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available