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Adhesion and invasion studies of uveal melanoma

Woodward, Julia Keren Lynda (2003) Adhesion and invasion studies of uveal melanoma. PhD thesis, University of Sheffield.

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Posterior uveal melanoma is the most common intraocular malignancy in adults. Metastasis occurs in approximately 50% of all cases, and spread is primarily to the liver. Very little is known about the factors that regulate uveal melanoma metastasis, and it possible that this tumour may follow Paget's 'seed and soil' hypothesis. Identification of further indicators associated with the metastatic phenotype, may aid in detecting patients most at risk. Using a series of short-term cultures, this study aimed to further identify factors that may be involved with uveal melanoma metastasis to the liver. Detachment of cells from the primary tumour mass requires changes to adhesive and degradative interactions. Uveal melanomas were shown to ubiquitously express some integrins, degradative enzymes and inhibitors, whilst expression of others (a 1, a2, a4, and a6) are more variable, and may in part be related to the in vitro stimulation. Once migrated through the surrounding matrix, and basement membrane, migration through the endothelium is essential. Using an in vitro model of transendothelial invasion, results indicated that for uveal melanoma, invasion seemed to correlate with a wider range of prognostic indicators, than through the basement membrane alone. Uveal melanoma cells may disseminate widely, but primarily initiate metastatic growth at the liver alone. Factors associated with uveal melanomas have been reported to assist in liver targeting, and similarly most uveal melanomas in this study responded positively to factors secreted by cells of hepatic origin. Cells derived from dermal tissues nevertheless also stimulated invasion. After coculture of uveal melanoma cells with dermal or hepatic endothelial cells, notable changes were however only observed through interactions with hepatic endothelial cells, suggesting that despite attraction to other sites, uveal melanomas may only arrest in the liver. In particular, an increase in uveal melanoma a4 expression, accompanied by an increase in hepatic endothelial VCAM-1 expression may be involved in liver targeting.

Item Type: Thesis (PhD)
Keywords: Cancer
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Medicine (Sheffield)
Other academic unit: Institute for Cancer Studies and Department of Ophthalmology and Orthoptics
Identification Number/EthosID: uk.bl.ethos.251213
Depositing User: EThOS Import Sheffield
Date Deposited: 28 Mar 2019 11:32
Last Modified: 28 Mar 2019 11:32
URI: http://etheses.whiterose.ac.uk/id/eprint/21740

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