Expression of polypeptide GalNAc-transferases in stratified epithelia and squamous cell carcinomas: immunohistological evaluation using monoclonal antibodies to three members of the GalNAc-transferase family

Mucin-type O-glycosylation is initiated by a large family of UDP-GalNAc: po lypeptide N-acetyl-galactosaminyltransferases (GalNAc-transferases). Indivi dual GalNAc-transferases appear to have different functions and Northern an alysis indicates that they are differently expressed in different organs. T his suggests that O-glycosylation may vary with the repertoire of GalNAc-tr ansferases expressed in a given cell. In order to study the repertoire of G alNAc-transferases in situ in tissues and changes in tumors, we have genera ted a panel of monoclonal antibodies (MAbs) with well defined specificity f or human GalNAc-T1, -T2, and -T3. Application of this panel of novel antibo dies revealed that GalNAc-transferases are differentially expressed in diff erent cell lines, in spermatozoa, and in oral mucosa and carcinomas. For ex ample, GalNAc-T1 and -T2 but not -T3 were highly expressed in WI38 cells, a nd GalNAc-T3 but not GalNAc-T1 or -T2 was expressed in spermatozoa, The exp ression patterns in normal oral mucosa were found to vary with cell differe ntiation, and for GalNAc-T2 and -T3 this was reflected in oral squamous cel l carcinomas. The expression pattern of GalNAc-T1 was on the other hand cha nged in tumors to either total loss or expression in cytological poorly dif ferentiated tumor cells, where the normal undifferentiated cells lacked exp ression. These results demonstrate that the repertoire of GalNAc-transferas es is different in different cell types and vary with cellular differentiat ion, and malignant transformation. The implication of this is not yet fully understood, but it suggests that specific changes in sites of O-glycosylat ion of proteins may occur as a result of changes in the repertoire of GalNA c-transferases.