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Inhibition of MT-450 rat mammary tumour growth by antibodies recognising subtypes of blood group antigen B

Abstract

Using subtractive immunization to identify cell surface epitopes expressed in a metastasis-specific fashion on cells of the rat MT-W9 mammary carcinoma model, we generated a monoclonal antibody called M-N#1. This antibody binds specifically to metastasizing cells of the MT-W9 series and also to certain other metastasizing rat mammary carcinoma cell lines. We demonstrate that the M-N#1 antibody recognizes a fucosylated N-glycosyl sugar modification, and furthermore show that the epitope specificity of the M-N#1 antibody is for blood group antigen B subtypes 2, 3 and 4 with slight cross-reactivity with blood group antigen A subtype 2. The expression of these carbohydrate epitopes on MT-450 cells is functionally important, because the M-N#1 antibody efficiently inhibits MT-450 tumour growth in spontaneous metastasis assays. These results suggest that expression of the subtypes of blood group antigen B recognized by the M-N#1 antibody does not directly participate in the metastatic cascade but rather confers a growth or survival advantage on the tumour cells.

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Acknowledgements

We thank Uschi Rahmsdorf and Anja Steffen for excellent technical assistance and Martin Hofmann for critically reading the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft (He 551/8-2) and Boehringer Ingelheim. JP Sleeman was supported by a European Union Marie Curie Fellowship.

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Sleeman, J., Kim, U., LePendu, J. et al. Inhibition of MT-450 rat mammary tumour growth by antibodies recognising subtypes of blood group antigen B. Oncogene 18, 4485–4494 (1999). https://doi.org/10.1038/sj.onc.1202808

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