Although disialyl glycosphingolipids such as GD3 and GD2 have been considered to be associated with malignant tumours, whether branched-type disialyl glycosphingolipids show such an association is not well understood. We investigated the sialyltransferases responsible for the biosynthesis of DSGG (disialylgalactosylgloboside) from MSGG (monosialylgalactosylgloboside). Among six GalNAc:α2,6-sialyltransferases cloned to date, we focused on ST6GalNAc III, V and VI, which utilize sialylglycolipids as substrates. In vitro enzyme analyses revealed that ST6GalNAc III and VI generated DSGG from MSGG with Vmax/Km values of 1.91 and 4.16 respectively. Transfection of the cDNA expression vectors for these enzymes resulted in DSGG expression in a renal cancer cell line. Although both ST6GalNAc III and VI genes were expressed in normal kidney cells, the expression profiles of ST6GalNAc VI among 20 renal cancer cell lines correlated clearly with those of DSGG, suggesting that the sialyltransferase involved in the synthesis of DSGG in the kidney is ST6GalNAc-VI. ST6GalNAc-VI and DSGG were found in proximal tubule epithelial cells in normal kidney tissues, while they were downregulated in renal cancer cell lines and cancer tissues. All these findings indicated that DSGG was suppressed during the malignant transformation of the proximal tubules as a maturation arrest of glycosylation.
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Research Article|
February 26 2007
Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: downregulation of ST6GalNAc VI in renal cancers
Motohiro Senda;
Motohiro Senda
*Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan
†Department of Urology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan
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Akihiro Ito;
Akihiro Ito
‡Department of Urology, Tohoku University Graduate School of Medicine, Seiryo, Aoba-ku, Sendai 980-8575, Japan
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Akiko Tsuchida;
Akiko Tsuchida
*Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan
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Tomoko Hagiwara;
Tomoko Hagiwara
§Department of Clinical Research, Nagoya National Hospital, Naka-ku, Nagoya 460-0001, Japan
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Tsuguhiro Kaneda;
Tsuguhiro Kaneda
§Department of Clinical Research, Nagoya National Hospital, Naka-ku, Nagoya 460-0001, Japan
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Yoko Nakamura;
Yoko Nakamura
*Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan
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Kenji Kasama;
Kenji Kasama
¶Department of Mass Analysis, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
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Makoto Kiso;
Makoto Kiso
∥Department of Applied Bio-organic Chemistry, Gifu University, Gifu 501-1193, Japan
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Kazuhiro Yoshikawa;
Kazuhiro Yoshikawa
**Department of Pathology, Aichi Medical School, Nagakute, Aichi 480-1195, Japan
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Yoko Katagiri;
Yoko Katagiri
††Department of Developmental Biology, National Research Institute for Child Health and Development, Taishido, Setagaya-ku, Tokyo 154-8567, Japan
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Yoshinari Ono;
Yoshinari Ono
†Department of Urology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan
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Manabu Ogiso;
Manabu Ogiso
*Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan
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Takeshi Urano;
Takeshi Urano
*Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan
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Keiko Furukawa;
Keiko Furukawa
*Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan
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Shinichi Oshima;
Shinichi Oshima
†Department of Urology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan
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Koichi Furukawa
Koichi Furukawa
1
*Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan
1To whom correspondence should be addressed (email koichi@med.nagoya-u.ac.jp).
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Publisher: Portland Press Ltd
Received:
July 21 2006
Revision Received:
November 06 2006
Accepted:
November 24 2006
Accepted Manuscript online:
November 24 2006
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2007
Biochem J (2007) 402 (3): 459–470.
Article history
Received:
July 21 2006
Revision Received:
November 06 2006
Accepted:
November 24 2006
Accepted Manuscript online:
November 24 2006
Citation
Motohiro Senda, Akihiro Ito, Akiko Tsuchida, Tomoko Hagiwara, Tsuguhiro Kaneda, Yoko Nakamura, Kenji Kasama, Makoto Kiso, Kazuhiro Yoshikawa, Yoko Katagiri, Yoshinari Ono, Manabu Ogiso, Takeshi Urano, Keiko Furukawa, Shinichi Oshima, Koichi Furukawa; Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: downregulation of ST6GalNAc VI in renal cancers. Biochem J 15 March 2007; 402 (3): 459–470. doi: https://doi.org/10.1042/BJ20061118
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