The role of SPARC in intestinal extracellular matrix changes and carcinogenesis

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The inflammatory bowel diseases (IBDs), Crohn s disease (CD) and ulcerative colitis (UC), are lifelong, chronic, incurable conditions and the number of patients being diagnosed with these conditions is increasing worldwide. Over recent years there has been the development of new treatments effective in controlling the chronic inflammation of the bowel in many of these patients. There is no evidence, however that these therapies reduce the rate of bowel scarring or the development of bowel cancer that complicated these conditions. Healing of the bowel inflammation can result in scarring. Whether scarring develops or not hinges on the balance between tissue production and destruction. If production outstrips destruction then scarring may occur, but if this balance can be modified in favour of reduced production then, potentially, healing may proceed without scarring. This project aims to investigate the role of a protein, SPARC, that can regulate scar formation and its interactions with other proteins that can alter scar formation in a mouse model of chronic bowel inflammation. Chronic inflammation of the bowel can also cause the development of colon cancer. Colon cancer is one of the most common cancers in the Australian population. The level of SPARC in the colon cancer at time of initial surgery may predict the risk of disease recurrence. The aim of this study is to determine if SPARC levels can identify those patients at higher risk of cancer recurrence. The role of SPARC will also be examined in a mouse model of colon cancer to determine if increased SPARC levels increased or decrease the rate of cancer growth and its spread.