Heparan sulfate undergoes specific structural changes during the progression from human colon adenoma to carcinoma in vitro.
AffiliationCancer Research Campaign Department, Medical Oncology, University of Manchester and Christie Hospital National Health Service Trust, Withington, Manchester M20 4BX, United Kingdom.
MetadataShow full item record
AbstractWe report a detailed analysis of heparan sulfate (HS) structure using a model of human colon carcinogenesis. Metabolically radiolabeled HS was isolated from adenoma and carcinoma cells. The chain length of HS was the same in both cell populations (Mr 20,000; 45-50 disaccharides), and the chains contained on average of two sulfated domains (S domains), identified by heparinase I scission. This enzyme produced fragments of approximate size 7 kDa, suggesting that the S domains were evenly spaced in the intact HS chain. The degree of polymer sulfation and the patterns of sulfation were strikingly different between the two HS species. When compared with adenoma HS, the iduronic acid 2-O-sulfate content of the carcinoma-derived material was reduced by 33%, and the overall level of N-sulfation was reduced by 20%. However, the level of 6-O-sulfation was increased by 24%, and this was almost entirely attributable to an enhanced level of N-sulfated glucosamine 6-O-sulfate, a species whose data implied was mainly located in the mixed sequences of alternating N-sulfated and N-acetylated disaccharides. The results indicate that in the transition to malignancy in human colon adenoma cells, the overall molecular organization of HS is preserved, but there are distinct modifications in both the S domains and their flanking mixed domains that may contribute to the aberrant behavior of the cancer cell.
CitationHeparan sulfate undergoes specific structural changes during the progression from human colon adenoma to carcinoma in vitro. 1998, 273 (1):51-7 J. Biol. Chem.
JournalJournal of Biological Chemistry
- Enterocytic differentiation correlates with changes in the fine structure and sulfation of perlecan in HT29 human colon carcinoma cells.
- Authors: Molist A, Romarís M, Villena J, Bassols A
- Issue date: 1997 Sep 29
- Interaction of thrombospondin-1 and heparan sulfate from endothelial cells. Structural requirements of heparan sulfate.
- Authors: Feitsma K, Hausser H, Robenek H, Kresse H, Vischer P
- Issue date: 2000 Mar 31
- Cell surface syndecan-1 on distinct cell types differs in fine structure and ligand binding of its heparan sulfate chains.
- Authors: Kato M, Wang H, Bernfield M, Gallagher JT, Turnbull JE
- Issue date: 1994 Jul 22
- A new model for the domain structure of heparan sulfate based on the novel specificity of K5 lyase.
- Authors: Murphy KJ, Merry CL, Lyon M, Thompson JE, Roberts IS, Gallagher JT
- Issue date: 2004 Jun 25
- Liver heparan sulfate structure. A novel molecular design.
- Authors: Lyon M, Deakin JA, Gallagher JT
- Issue date: 1994 Apr 15