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M211034200v1
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Papers In Press, published online ahead of print March 31, 2003
J. Biol. Chem, 10.1074/jbc.M211034200
Submitted on October 29, 2002
Revised on March 17, 2003
Accepted on March 31, 2003

Synthesis of disialyl Lewis a structure in colon cancer cell lines by a sialyltransferase ST6GalNAc VI responsible for the synthesis of alpha -series gangliosides

Akiko Tsuchida, Tetsuya Okajima, Keiko Furukawa, Takayuki Ando, Hideharu Ishida, Aruto Yoshida, Yoko Nakamura, Reiji Kannagi, Makoto Kiso, and Koichi Furukawa

Department of Biochemistry II, Nagoya University School of Medicine, Nagoya 466-0065

Corresponding Author: koichi{at}med.nagoya-u.ac.jp

Biosynthesis of disialyl Lewis a (Lea) was analyzed using previously-cloned ST6GalNAc V and ST6GalNAc VI, which were responsible for the synthesis of alpha -series gangliosides. Among lactotetraosylceramide (Lc4), neolactotetraosyl-ceramide (nLc4) and their sialyl forms, only sialyl Lc4 was sialylated with ST6GalNAc V and ST6GalNAc VI. The products were confirmed to be disialyl Lea in TLC-immunostaining. Compared with the original substrate GM1b, the synthetic rates of disialyl Lea were 22% and 38% with ST6GalNAc V and ST6GalNAc VI, respectively. Since sialyl Lea could not be converted to disialyl Lea, disialyl Lea was produced only from disialyl Lc4. Therefore, it appears that ST6GalNAc V/VI and fucosyltransferase III (FUT-3) compete for sialyl Lc4, their common substrate. The results of either one or co-transfection of two genes into Cos 1 cells revealed that both ST6GalNAc VI and FUT-3 contributed in the synthesis of disialyl Lea, but partly compete each other. Many colon cancer cell lines expressed ST6GalNAc VI gene more or less, and some of them actually expressed disialyl Lea. None of them expressed ST6GalNAc V. These results suggested the novel substrate specificity of ST6GalNAc VI, that is responsible for the synthesis of disialyl Lea, but not for alpha -series gangliosides in human colon tissues.


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 J BiochemHome page
A. Tsuchida, M. Ogiso, Y. Nakamura, M. Kiso, K. Furukawa, and K. Furukawa
Molecular Cloning and Expression of Human ST6GalNAc III: Restricted Tissue Distribution and Substrate Specificity
J. Biochem., September 1, 2005; 138(3): 237 - 243.
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K. Miyazaki, K. Ohmori, M. Izawa, T. Koike, K. Kumamoto, K. Furukawa, T. Ando, M. Kiso, T. Yamaji, Y. Hashimoto, et al.
Loss of Disialyl Lewisa, the Ligand for Lymphocyte Inhibitory Receptor Sialic Acid-Binding Immunoglobulin-Like Lectin-7 (Siglec-7) Associated with Increased Sialyl Lewisa Expression on Human Colon Cancers
Cancer Res., July 1, 2004; 64(13): 4498 - 4505.
[Abstract] [Full Text] [PDF]


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