Expression and localisation of MUC1 modified with sialylated core-2 O-glycans in mucoepidermoid carcinoma

Author:

Sugiura Takanori1,Hashimoto Kazuhiko2,Kikuta Kazutaka3,Anazawa Ukei4,Nomura Takeshi1,Kameyama Akihiko5

Affiliation:

1. Department of Oral Oncology, Oral and Maxillofacial Surgery, Ichikawa General Hospital, Tokyo Dental College

2. Department of Pathology and Laboratory medicine, Ichikawa General Hospital, Tokyo Dental College

3. Department of Musculoskeletal Oncology and Orthopaedic Surgery, Tochigi Cancer Center

4. Department of Orthopaedic Surgery, Ichikawa General Hospital, Tokyo Dental College

5. Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)

Abstract

Abstract Mucoepidermoid carcinoma (MEC) is the most frequent of the rare salivary gland malignancies. We previously reported high expression of Mucin 1 (MUC1) modified with sialylated core-2 O-glycans in MEC by using tissue homogenates. In this study, we characterised glycan structures of MEC and identified the localisation of cells expressing these distinctive glycans on MUC1. Mucins were extracted from the frozen tissues of three patients with MEC, and normal salivary glands (NSGs) were extracted from seven patients, separated by supported molecular matrix electrophoresis (SMME) and the membranes stained with various lectins. In addition, formalin-fixed, paraffin-embedded sections from three patients with MEC were subjected to immunohistochemistry (IHC) with various monoclonal antibodies and analysed for C2GnT-1 expression by in situ hybridisation (ISH). Lectin blotting of the SMME membranes revealed that glycans on MUC1 from MEC samples contained α2,3-linked sialic acid. In IHC, MUC1 was diffusely detected at MEC-affected regions but was specifically detected at apical membranes in NSGs. ISH showed that C2GnT-1 was expressed at the MUC1-positive in MEC-affected regions but not in the NSG. Conclusion: MEC cells produced MUC1 modified with α2,3-linked sialic acid-containing core 2 O-glycans. MUC1 containing these glycans deserves further study as a new potential diagnostic marker of MEC. (200 words)

Publisher

Research Square Platform LLC

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