Tn antigen is a pre-cancerous biomarker in breast tissue and serum in N-nitrosomethylurea-induced rat mammary carcinogenesis

The Tn determinant (GalNAc alpha-O-Ser/Thr), normally a cryptic structure i n mucin-type O-glycans, is a tumor-associated marker which has attracted pa rticular interest in cancer biology. We herein report the characterization of N-nitro-somethylurea (NMU)-induced breast cancer in rats as a new model for the study of aberrant O-glycosylation products. Tn-antigen expression i s detectable not only in mammary carcinoma induced by NMU but also in carci nogen-initiated mammary epithelium, indicating that Tn could be a precancer ous biomarker in rats treated with NMU, Serum Tn levels were followed up lo ngitudinally in 30 rats from the time of the first injection of NMU to the development of advanced breast cancer. Tn antigen increased in serum severa l weeks before tumor development, and became highly positive after 56 days of carcinogenesis (prior to breast-cancer occurrence), and the levels corre lated with Tn expression in mammary tissues. However, during the follow-up after detection of mammary cancer, all animals displayed a significant decr ease of serum Tn antigen, and low levels were observed in animals with adva nced breast cancer. We have shown that the humoral immune response to cance r, with the production of anti-Tn antibodies, could hamper the detection of Tn antigen in animals with advanced breast cancer. These results suggest t hat NMU-induced rat mammary carcinogenesis is a useful experimental model t o study the regulation of O-glycosylation at the cellular level during mali gnant transformation. (C) 2000 Wiley-Liss, Inc.