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Human Colon Adenocarcinomas Express a MUC1-associated Novel Carbohydrate Epitope on Core Mucin Glycans Defined by a Monoclonal Antibody (A10) Raised against Murine Ehrlich Tumor Cells¹

Hospital Clínico San Carlos, Universidad Complutense, E-28040 Madrid [M. M., D. V., J. A. A., J. G., J. L. S.]; Facultat de Medicina, Dept. Biologia Celular, IDIBAPS Universitat de Barcelona, E-08028 Barcelona [G. E.]; and Institut Municipal d’Investigació Médica, Universitat Pompeu Fabra, E-08003 Barcelona [F. X. R.], Spain

ABSTRACT

A monoclonal antibody (mAb; A10) raised against murine Ehrlich tumor cell surface carbohydrates was tested for reactivity with human normal and malignant tissues. A10 reacted strongly, with a high proportion of adenocarcinomas arising from colon and other tissues but not with breast carcinomas or other malignant tumors. Normal tissues were virtually A10 unreactive, except for the duct cells from breast and pancreas and some bronchial mucosae. Ultrastructural studies showed mAb A10 immunolabeling of both microvilli and mucin droplets in colon cancer cells but not in normal absorptive or globet cells. A10 reacted strongly with mucin-enriched fractions from colon cancer tissues and HT-29 xenografts but not from normal colon tissues. A10 epitope was carried on MUC1 derived from colon adenocarcinomas and probably on other mucin species, although not on MUC2 molecules. A10 epitope was resistant to exoglycosidases and periodate oxidation but sensitive to the Smith’s degradation and ß-elimination, suggesting the involvement of O-linked carbohydrates in nonterminal reducing positions. A mucin-type glycosidic linkage was supported because of the lack of A10 reactivity with HT-29 cells grown with phenyl-N-acetyl--D-galactosaminide. Deglycosylation studies with trifluoromethanesulfonic acid pointed to the involvement of core mucin glycans in the A10 epitope. This epitope was resistant to protease, O- and N-glycanase treatments carried out on trifluoromethanesulfonic acid-deglycosylated mucins. Inhibition studies with core 1, core 2, core 3, and core 6 suggested the latter [GlcNAcß(1–6)GalNAc] as being involved in A10 epitope. Taken together, the present results point to A10 defining a core 6-related epitope on core mucin glycans expressed by colon cancer MUC1 not previously associated with human cancer.

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