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.
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:alpha2,6-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 V(max)/K(m) 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.
Senda
Motohiro
M
Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
Ito
Akihiro
A
Tsuchida
Akiko
A
Hagiwara
Tomoko
T
Kaneda
Tsuguhiro
T
Nakamura
Yoko
Y
Kasama
Kenji
K
Kiso
Makoto
M
Yoshikawa
Kazuhiro
K
Katagiri
Yoko
Y
Ono
Yoshinari
Y
Ogiso
Manabu
M
Urano
Takeshi
T
Furukawa
Keiko
K
Oshima
Shinichi
S
Furukawa
Koichi
K
D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation; D005732:Gangliosides / Q000096:biosynthesis*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006028:Glycosphingolipids / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000145:classification / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000201:enzymology*; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007700:Kinetics; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics; D012799:Sialyltransferases / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D005732:Gangliosides; D006028:Glycosphingolipids; D007527:Isoenzymes; D012333:RNA, Messenger; C086047:disialosyl galactosyl globoside; C476449:GalNAc sialyltransferase VI; D012799:Sialyltransferases