Expression of Sia alpha 2-->6Gal beta 1-->4GlcNAc residues on sugar chains of glycoproteins including carcinoembryonic antigens in human colon adenocarcinoma: applications of Trichosanthes japonica agglutinin I for early diagnosis.

The N-linked sugar chain structures of the carcinoembryonic antigen (CEA) produced by liver metastases of colon cancers and the normal counterpart of CEA purified from human adult feces (NFA-2) were previously determined comparatively (K. Fukushima, T. Ohkura, M. Kanai, M. Kuroki, Y. Matsuoka, A. Kobata, and K. Yamashita. Glycobiology, 5:105-115, 1995). Seventy-five % of NFA-2 contained complex type sugar chains with Gal beta 1-->3GlcNAc residues, in contrast to the sugar chains of CEA, in which over 90% of the oligosaccharides contained Gal beta 1-->4GlcNAc residues, and Sia alpha 2-->6Gal beta 1-->4GlcNAc residues were detected in 18 to 65% of the oligosaccharides. The expression of Sia alpha 2-->6Gal beta 1-->4GlcNAc residues on CEA molecules in sera and tissues was investigated using Trichosanthes japonica agglutinin I (TJA-I), which interacts with Sia alpha 2-->6Gal beta 1-->4 GlcNAc residues. Ten purified CEA samples bound to a TJA-I column while seven NFA-2 samples passed through the column. Various concentrations of serum CEA samples from patients with metastatic colon cancers exclusively bound to the TJA-I column, reflecting that CEA molecules exfoliated into the blood circulation comprise sugar chains with Sia alpha 2-->6Gal beta 1-->4GlcNAc residues. In histochemical studies involving biotinylated TJA-I, normal mucosa (n = 20) and benign adenomas (n = 20) were not stained, and 83% of well and moderately differentiated colon adenocarcinomas (n = 53) reacted with TJA-I, although poorly differentiated ones (n = 9) and mucinous specimens (n = 10) were negative. Because over 90% of colon adenocarcinomas can be differentiated, TJA-I staining might be applicable to the early diagnosis of colon cancers.