Abstract
BackgroundFascin is associated with increased cell motility in colorectal tumours but is absent from the normal colonic epithelium. We examined the expression of fascin in inflammatory bowel disease (IBD) and its location at regions undergoing restitution and regeneration. Tissue repair is essential for disease remission and we sought to determine the effects of therapeutic modalities on fascin expression and function using an in vitro model.MethodsImmunohistochemistry was performed on colonic tissue from IBD patients to determine changes in fascin expression and distribution. A human colorectal epithelial cell line was treated with 5-aminosalicylate (a common treatment for IBD), or sodium butyrate to determine the effect on fascin expression and cell motility.ResultsFascin overexpression was observed in both ulcerative colitis and Crohn's colitis and expression correlated with disease severity. Immunoreactivity was more intense and widespread in Crohn's compared to ulcerative colitis. Interestingly, highly expressing foci were consistently observed at the edges of ulcers where flattened, motile epithelial cells are actively involved in restitution, and also in areas of mucosal regeneration.5-aminosalicylate reduced fascin expression in colorectal epithelial cells and inhibited their motility. Conversely, sodium butyrate increased fascin expression and stimulated cell motility in the same cells.ConclusionsOur data shows that fascin is overexpressed in inflammatory bowel disease and its location is indicative of a role in tissue repair. Our in vitro studies show that different therapeutic modalities may have converse effects on fascin expression and may have significant consequences for disease remission and the clinical management of IBD.
Highlights
Fascin is associated with increased cell motility in colorectal tumours but is absent from the normal colonic epithelium
Fascin expression is expressed in inflamed colonic epithelium Previous studies have shown that fascin is not expressed in the epithelial cells of the normal colonic mucosa, but is broadly expressed in the endothelial cells, fibroblasts and infiltrating lymphocytes of the lamina propria and submucosa [11,12]
Our previous study of colorectal adenomas showed epithelial fascin expression focussed around the tumour stalk, provoking the hypothesis that fascin expression may be modulated by inflammatory mediators [12]
Summary
Fascin is associated with increased cell motility in colorectal tumours but is absent from the normal colonic epithelium. We examined the expression of fascin in inflammatory bowel disease (IBD) and its location at regions undergoing restitution and regeneration. UC exclusively affects the large intestine, whereas CD affects the colon in 60% of cases (known as Crohn’s colitis), but can involve other parts of the GI tract [1]. These common, chronic and debilitating conditions remain incurable, with their aetiology and pathogenesis not clearly understood. Long-term illness greatly increases the risk of colorectal cancer, which causes approximately 15% of all IBD patient deaths [2]. Even the distinction between low grade- and high-grade dysplasia provides little indication of disease outcome [2] and there is, an urgent need for biomarkers to predict neoplasia in IBD
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