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Different modes of sialyl-Tn expression during malignant transformation of human colonic mucosa

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Abstract

Monoclonal antibodies TKH2 and B72.3, which react with the mucin-associated sialyl-Tn(STn) antigen, preferentially bind to cancerous but not normal colonic tissues. If O-acetyl groups are removed by saponification of tissues, MAb TKH2 will react with normal colonocytes, whereas MAb B72.3 remains non-reactive. To explain this difference in binding specificity, we tested both MAbs against synthetic constructs of single (monomeric) or clustered (trimeric) STn epitopes by enzyme immunoassay. Both MAb TKH2 and MAb B72.3 reacted with trimeric STn, but MAb TKH2 demonstrated greater binding than MAb B72.3 to monomeric STn. This suggests that normal colonic mucosa expresses monomeric STn epitopes, but that with transformation to malignancy, clustered STn epitopes appear. The appearance of clustered STn epitopes during colonic carcinogenesis represents a novel pattern of carbohydrate antigen expression and implicates alterations at the level of apomucins and/or glycosyltransferases responsible for cluster epitope formation.

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Authors and Affiliations

  1. Gastrointestinal Research Laboratory, Department of Medicine, Mount Sinai School of Medicine, NYC, NY, 10029, USA

    Shunichiro Ogata, Anli Chen, Carmen Perez & Steven H. Itzkowitz

  2. Biomira, Inc., Edmonton Research Park, 2011 94 Street, Edmonton, Canada, T6N 1H1

    Rao Koganty, Mark Reddish & B. Michael Longenecker

Authors
  1. Shunichiro Ogata
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  2. Rao Koganty
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  3. Mark Reddish
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  4. B. Michael Longenecker
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  5. Anli Chen
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  6. Carmen Perez
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  7. Steven H. Itzkowitz
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Ogata, S., Koganty, R., Reddish, M. et al. Different modes of sialyl-Tn expression during malignant transformation of human colonic mucosa. Glycoconj J 15, 29–35 (1998). https://doi.org/10.1023/A:1006935331756

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