The Tn determinant (GalNAcalpha-O-Ser/Thr), normally a cryptic structure in
mucin-type O-
glycans, is a
tumor-associated marker which has attracted particular interest in
cancer biology. We herein report the characterization of N-
nitrosomethylurea (NMU)-induced
breast cancer in rats as a new model for the study of aberrant O-glycosylation products.
Tn-antigen expression is detectable not only in mammary
carcinoma induced by NMU but also in
carcinogen-initiated mammary epithelium, indicating that Tn could be a pre-cancerous
biomarker in rats treated with NMU. Serum Tn levels were followed up longitudinally in 30 rats from the time of the first injection of NMU to the development of advanced
breast cancer.
Tn antigen increased in serum several weeks before
tumor development, and became highly positive after 56 days of
carcinogenesis (prior to
breast-cancer occurrence), and the levels correlated with Tn expression in mammary tissues. However, during the follow-up after detection of
mammary cancer, all animals displayed a significant decrease of serum
Tn antigen, and low levels were observed in animals with advanced
breast cancer. We have shown that the humoral immune response to
cancer, with the production of anti-Tn
antibodies, could hamper the detection of
Tn antigen in animals with advanced
breast cancer. These results suggest that NMU-induced rat mammary
carcinogenesis is a useful experimental model to study the regulation of O-glycosylation at the cellular level during malignant transformation.