A
glycolipid detected in human gastric mucosa with anti-GM2
monoclonal antibody was characterized to be GalNAc beta 1-4[NeuAc alpha 2-3]Gal beta 1-4GlcNAc beta 1-3Gal 1-4Glc-Cer (NGM-1), which was lost in
gastric cancer tissue with complementary increase of GM2 sharing the same terminal
carbohydrate structure as
NGM-1 (Dohi, T., Ohta, S., Hanai, N., Yamaguchi, K., and Oshima, M. (1990) J. Biol. Chem. 265, 7880-7885). The study on differential expression of
NGM-1 in gastric fundic mucosa, pyloric mucosa, gastric
cancer, and various other tissues indicated that
NGM-1 existed specifically in fundic mucosa. The content of GM3 and sialylparagloboside (SPG), which are the substrates for the synthesis of GM2 and
NGM-1, respectively, were not significantly different in these tissues. Therefore, the presence of two kinds of beta 1,4GalNAc
transferases having different substrate specificity was considered to be critical for the expression of
NGM-1 and GM2. The activity of beta 1,4GalNAc
transferase which synthesizes GM2 or
NGM-1 was determined by detecting the products with specific
monoclonal antibodies. The activity of beta 1,4GalNAc transfer to SPG was high in fundic mucosa, while it was absent in pyloric mucosa or
cancer. On the other hand, the increased activity of beta 1,4GalNAc transfer to GM3 was observed in
cancer tissues and
cancer cell lines which were rich in GM2. Our conclusion is that the limited expression of
NGM-1 in fundic mucosa and the increase of GM2 in
cancer are attributed to two types of beta 1,4GalNAc
transferases localized in each region with different substrate specificity; the one in fundic mucosa transfers GalNAc to SPG but not to GM3, and the other one enhanced in
cancer transfers GalNAc to GM3 but not to SPG.