Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Esophageal squamous carcinoma and normal squamous epithelia express differentially glycosylated mucin 21 (#89)

Yuan Tian 1 , Kaori Denda-Nagai 1 , Mika Kamata-Sakurai 1 , Shoji Nakamori 2 , Tatsuro Irimura 1
  1. The University of Tokyo, Bunkyo-ku, Tokyo, Japan
  2. National Hospital Organization Osaka National Hospital, Osaka, Japan

Aberrant glycosylation occurs in essentially all types of experimental and human cancers. Many glycosyl epitopes constitute tumor-associated antigens, and mucin with aberrant glycoforms has been known to involve cancer progression and metastasis. However, there are few reports of the association between the glycosylation of mucins and squamous carcinoma. Here, we show that human mucin 21 (MUC21) could be used as a marker of squamous carcinoma in esophagus.
Monoclonal antibodies (mAbs) against mucin 21 (MUC21), a human counterpart of mouse epiglycanin/Muc21, were prepared using human embryonic kidney 293 cells transfected with MUC21 as the immunogen. The specificity of these mAbs was examined by flow cytometry, immunoprecipitation, and Western blotting, focusing on the differential glycosylation of MUC21 expressed in variant Chinese hamster ovary (CHO) cells (ldlD cells and Lec2 cells) and CHO-K1 cells. One of these mAbs, heM21D, bound to both the unmodified core polypeptide of MUC21 and MUC21 attached with N-acetylgalactosamine (Tn-MUC21). Six antibodies, including mAb heM21C, bound to MUC21 with Tn, T, or sialyl-T epitopes but not the unmodified core polypeptide of MUC21. Esophageal squamous carcinomas and adjacent squamous epithelia were immunohistochemically examined for the binding of these mAbs. MUC21 was expressed in esophageal squamous epithelial cells, and its O-glycan extended forms were observed in the luminal portions of squamous epithelia. As revealed by the binding of mAb heM21D and the absence of reactivity with mAb heM21C, esophageal squamous carcinoma cells produce MUC21 without the attachment of O-glycans. This is the first report to show that there is a change in the glycoform of MUC21 that can be used to differentiate between squamous epithelia and squamous carcinoma of the esophagus. Thus, these antibodies represent a useful tool to characterize squamous epithelial differentiation and carcinogenesis.
This work was supported in part by Global COE Program “Medical System Innovation on Multidisciplinary Integration” from MEXT, Japan.