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

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 cert...

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Veröffentlicht in:Oncogene 1999-08, Vol.18 (31), p.4485-4494
Hauptverfasser: SLEEMAN, J. P, KIM, U, LEPENDU, J, HOWELLS, N, COQUERELLE, T, PONTA, H, HERRLICH, P
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Sprache:eng
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Zusammenfassung: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.
ISSN:0950-9232
1476-5594
DOI:10.1038/sj.onc.1202808