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The clinical relevance of pigment epithelium3 derived factor(PEDF)in wound healing and colorectal cancer

Harries, Rhiannon 2017. The clinical relevance of pigment epithelium3 derived factor(PEDF)in wound healing and colorectal cancer. MD Thesis, Cardiff University.
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Abstract

There are similarities between tissue repair and cancer development. Epithelial tumours promote the formation of the stroma by activation of the wound healing process, but unlike healing wounds the process is not self-limiting. Pigment epithelium derived factor(PEDF)is a secreted glycoprotein that has been shown to exhibit multiple biological properties including anti-angiogenesis, anti-tumorigenesis and immune-modulation. Previous studies demonstrated that PEDF expression is downregulated as prognostic factors worsen in a range of cancers and chronic inflammatory conditions and treatment with recombinant PEDF has showed some benefit in cellular functional models. However, there has been little evidence to date to assess the role of PEDF in colorectal cancer and wound healing. The aims of this study were to elucidate more detailed regulatory mechanisms of PEDF in wound healing, and tumour angiogenesis in colorectal cancer and provide evidence to develop PEDF or its fragments as therapeutics for wound healing or colorectal cancer treatment. This study found that PEDF expression was down regulated in colorectal cancer cell lines and tissue and that treatment with recombinant PEDF resulted in significant decreases in the rate of colorectal cancer cellular migration and invasion and an increase in cellular adhesion in some colorectal cancer cell lines examined, suggesting a promising role of the treatment of PEDF in the prevention of colorectal cancer metastatic spread. Within wound healing, our results indicated that PEDF expression was high amongst dermal fibroblasts but less so in keratinocytes and endothelial cell lines, suggesting that fibroblasts are responsible for secretion of PEDF in response to inflammation. In cellular functional models, recombinant PEDF treatment significantly increased the migration of keratinocytes, suggesting a possible role as a chronic wound treatment. Further studies are warranted to assess the role of PEDF in a range of colorectal cancer subsets, other wound healing cells and animal models to identify a suitable delivery vector.

Item Type: Thesis (MD)
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 9 October 2017
Last Modified: 09 Oct 2017 12:59
URI: http://orca-mwe.cf.ac.uk/id/eprint/105300

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