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Expression of Vicia villosa agglutinin (VVA)-binding glycoprotein in primary breast cancer cells in relation to lymphatic metastasis: is atypical MUC1 bearing Tn antigen a receptor of VVA?

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Summary

Aberrant carbohydrate expression frequently occurs in breast cancer and may endow cells with metastatic potential. Here we first studied the relationship between expression of Vicia villosa agglutinin (lectin) (VVA)-binding carbohydrates and aggressive breast cancer. We then investigated the molecular characteristics of these glycoproteins and compared them with those of glycoproteins recognized by the mouse anti-Tn monoclonal antibody (MAb) HB-Tn1. Histochemical studies of samples from 322 cases of invasive ductal carcinoma demonstrated that VVA-binding carbohydrate expression correlated with tumor stage, lymphatic invasion, and lymph node metastasis (p=0.0385, p=0.0019, and p=0.0430. respectively). Western blotting analysis of frozen materials from 39 cases, under denaturing and reducing conditions, revealed that the major cancer cell-specific VVA-binding proteins were molecules of about 30, 33, and >200 kDa. Cases expressing the ∼33 kDa molecule had significant lymphatic invasion more frequently than did cases not expressing this molecule (p=0.0076). Binding of VVA to the ∼30 and ∼33 kDa molecules was completely lost by preincubation of VVA with 1 mM Tn antigen (N-acetylgalactosamine α1- O-serine). The VVA-binding molecules appeared to react with VU-3C6 anti-MUC1 MAb. Expression of HB-Tn1 in breast cancer cells showed significant correlation with expression of VVA-binding carbohydrate(s) (p<0.0001) but HB-Tn1 reactivity was not clearly related to breast cancer aggressiveness. Because anti-Tn MAbs bound to Tn antigen clusters, we concluded that atypical MUC1 bearing the noncluster form of Tn antigen is implicated in aggressive growth of primary breast cancer cells, particularly in lymphatic metastasis.

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Acknowledgements

This work was supported in part by a Grant-in-Aid for Cancer Research [15–21] from the Ministry of Health, Labour and Welfare of Japan (T.K).

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Authors and Affiliations

  1. Second Department of Pathology, School of Medicine, Fukushima Medical University, Fukushima, Japan

    Takanori Kawaguchi

  2. Department of Pathology, Chiba National Hospital, Chiba, Japan

    Hiroshi Takazawa

  3. Nara Prefectural Institute of Public Health, Nara, Japan

    Shunsuke Imai

  4. Laboratory Animal Center, Osaka Medical College, Takatsuki, Osaka, Japan

    Junji Morimoto

  5. Second Department of Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan

    Takanori Watanabe & Masahiko Kanno

  6. Department of Pathology, Tochigi Cancer Center, Utsunomiya, Japan

    Seiji Igarashi

  7. School of Medicine, Fukushima Medical University, 1 Hikariga-Oka, 960-1295, Fukushima, Japan

    Takanori Kawaguchi

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  1. Takanori Kawaguchi
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  2. Hiroshi Takazawa
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  3. Shunsuke Imai
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  5. Takanori Watanabe
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Correspondence to Takanori Kawaguchi.

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Kawaguchi, T., Takazawa, H., Imai, S. et al. Expression of Vicia villosa agglutinin (VVA)-binding glycoprotein in primary breast cancer cells in relation to lymphatic metastasis: is atypical MUC1 bearing Tn antigen a receptor of VVA?. Breast Cancer Res Treat 98, 31–43 (2006). https://doi.org/10.1007/s10549-005-9115-6

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