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    Heparan sulfate undergoes specific structural changes during the progression from human colon adenoma to carcinoma in vitro.

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    Authors
    Jayson, Gordon C
    Lyon, Malcolm
    Paraskeva, C
    Turnbull, Jeremy E
    Deakin, Jon A
    Gallagher, John T
    Affiliation
    Cancer Research Campaign Department, Medical Oncology, University of Manchester and Christie Hospital National Health Service Trust, Withington, Manchester M20 4BX, United Kingdom.
    Issue Date
    1998-01-02
    
    Metadata
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    Abstract
    We 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.
    Citation
    Heparan sulfate undergoes specific structural changes during the progression from human colon adenoma to carcinoma in vitro. 1998, 273 (1):51-7 J. Biol. Chem.
    Journal
    Journal of Biological Chemistry
    URI
    http://hdl.handle.net/10541/92039
    DOI
    10.1074/jbc.273.1.51
    PubMed ID
    9417046
    Type
    Article
    Language
    en
    ISSN
    0021-9258
    ae974a485f413a2113503eed53cd6c53
    10.1074/jbc.273.1.51
    Scopus Count
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    All Christie Publications
    All Paterson Institute for Cancer Research

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