THE EXPRESSION OF ONCOFETAL ANTIGENS ON MUCINS OF HUMAN AMNIOTIC FLUID

Abstract

The relative high abundance of O-linked oligosaccharides on the mucin-type glycoproteins has opened a favorable perspective for detailed studies of carbohydrate epitope structures, which may be involved in processes relevant for cellular differentiation in development and oncogenesis. Immunological experiments, in particular those with monoclonal antibodies raised against the cell surfaces, have been sucessfully performed in order to monitor qualitatively oncofetal carbohydrate antigens and the changes in their patterns during such processes (1). On the other hand the biosynthetic studies on glycosyltransferases responsible for assembly of complex carbohydrates bound to proteins and their substrates lead to the conclusion, that several enzymes compete for a common substrate of specific structure available in the respective cellular compartment at the certain phase of biosynthesis (2). Therefore some carbohydrate microheterogeneity arising from the presence of different terminal epitope structures as well as the different branch length and different branching patterns on the single glycan attachment site should be expected. The structures of the O-linked glycans, liberated from the mucin-type glycoproteins by reductive elimination can be determined by spectroscopic methods, using different techniques of nuclear magnetic resonance (NMR) (3) and mass spectrometry (4). By combining the immunological and spectroscopic approach numerous oncofetal carbohydrate antigen structures have been found not only on mucins of developing systems (5), but on mucins of human body fluids of normal individuals like in seminal plasma (6) and milk (7) as well. Oncofetal antigens, recognized by a number of monoclonal antibodies like C-50, NS 19-9, OC 125, Leu Ml, 49 H 8 and 115 C 2, are strongly expressed also in the mucine fraction of human amniotic fluid (8). These were analysed by fast atom bombardment mass spectrometry (FAB-MS) (9), in particular Suitable for the determination of carbohydrate sequences, their branching patterns and their molecular size in native and derivatized samples, even in complex mixtures.