title: Altered glycosylation in inflammatory bowel disease: a possible role in cancer development.
abstract: Ulcerative colitis and Crohn's disease (together known as Inflammatory Bowel Disease or IBD) are both associated with increased risk for colorectal cancer. Although it is conventional to emphasise differences between IBD-associated and sporadic colon cancer, such as a lower rate of Adenomatosis Polyposis Coli mutations and earlier p53 mutations, IBD-associated cancer has a similar dysplasia-cancer sequence to sporadic colon cancer, similar frequencies of major chromosomal abnormalities and of microsatellite instability and similar glycosylation changes. This suggests that IBD-associated colon cancer and sporadic colon cancer might have similar pathogenic mechanisms. Because the normal colon is arguably in a continual state of low-grade inflammation in response to its microbial flora, it is reasonable to suggest that both IBD-associated and sporadic colon cancer may be the consequence of bacteria-induced inflammation. We have speculated that the glycosylation changes might result in recruitment to the mucosa of bacterial and dietary lectins that might otherwise pass harmlessly though the gut lumen. These could then lead to increased inflammation and/or proliferation and thence to ulceration or cancer. The glycosylation changes include increased expression of onco-fetal carbohydrates, such as the galactose-terminated Thomsen-Friedenreich antigen (Gal beta1,3GalNAc alpha-), increased sialylation of terminal structures and reduced sulphation. These changes cannot readily be explained by alterations in glycosyltransferase activity but similar changes can be induced in vitro by alkalinisation of the Golgi lumen. Consequences of these changes may be relevant not only for cell-surface glycoconjugates but also for intracellular glycoconjugates.
authors.affiliation: Glycobiology Group, Henry Wellcome Laboratory of Molecular & Cellular Gastroenterology, Department of Medicine, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK. bjcampbl@liverpool.ac.uk
authors.forename: B J
authors.initials: BJ
authors.lastname: Campbell
authors.forename: L G
authors.initials: LG
authors.lastname: Yu
authors.forename: J M
authors.initials: JM
authors.lastname: Rhodes
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D003110:Colonic Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006031:Glycosylation; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D012307:Risk Factors
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; C016467:Thomsen-Friedenreich antigen