Human α2,3-Sialyltransferase (ST3Gal II) Is a Stage-specific Embryonic Antigen-4 Synthase

Abstract

Monosialosyl globopentaosylceramide (MSGb5), originally described as stage-specific embryonic antigen-4, is expressed in testicular germ cell tumors and in aggressive cases of human renal cell carcinoma (RCC). Clarification of the molecular mechanisms regulating synthesis of MSGb5 is very important to understand testicular carcinogenesis and the malignant progression of human RCC. For this purpose, we have investigated alpha2,3-sialyltransferase involved in the synthesis of MSGb5. We used the method of expression cloning combined with polymerase chain reaction targeted to sialylmotif to isolate a cDNA clone from RCC cell line ACHN library. The cloned cDNA was found to be identical to the previously cloned ST3Gal II in sequence. A soluble recombinant form of the protein in COS-1 cells showed an enzyme activity of alpha2,3-sialyltransferase toward globopentaosylceramide (Gb5) in addition to asialo-GM1 and GM1a. Transient transfection of COS-7 and ACHN cells with this cDNA induced an increase of MSGb5, whereas stable transfection of antisense ST3Gal II cDNA suppressed expression of MSGb5 in ACHN cells. The ST3Gal II mRNA level was increased in 7 of 8 RCC cell lines and in all six RCC tissues surgically obtained, although it was not necessarily consistent with the MSGb5 level in RCC cell lines. This study indicates that ST3Gal II is a MSGb5 (stage-specific embryonic antigen-4) synthase and that its increased expression level is closely related to renal carcinogenesis.

Stage-specific embryonic antigen-4 as a potential therapeutic target in glioblastoma multiforme and other cancers

“…This result, together with the observation of Globo H expression in only six of the GBM cell lines we tested, indicates that SSEA-4 is the major globo-series GSL in GBM and that, once SSEA-3 is synthesized, it is converted efficiently to SSEA-4 (24). It has been suggested that an α2,3-sialyltransferase, encoded by ST3GAL2 gene, is the major SSEA-4 synthase that is closely related to renal carcinogenesis (36) and that the mRNA level of ST3GAL2 is increased in renal and colorectal carcinomas (37). We also observed that the mRNA level of ST3GAL2, but not of fucosyltransferase (FUT) 1 and 2, is abundant in GBM cell lines (Fig.…”

Adult onset cardiac dilatation in a transgenic mouse line with Gal.BETA.1,3GalNAc .ALPHA.2,3-sialyltransferase II (ST3Gal-II) transgenes: a new model for dilated cardiomyopathy

“…Complicated effects of exogenous ST3Gal-II are also suggested by transfection experiments of human ST3Gal-II in cell cultures. 24) In the experiments, the level of ST3Gal-II mRNA are not necessary consistent with those of monosialosyl globopentaosylceramide (MSGb5), a product catalyzed by ST3Gal-II. 24) Production of MSGb5 is highly dependent on cell types used for transfection, which may be due to cell-type-dependent sialidase activities.…”

Glycosphingolipid Functions

“…4-8-cell embryo blastomeres erythrocytes, mouse kidney, astrocytes, oviduct, edometrium and epididymis human granulocytes, renal tumors, glioblastoma initiating cells Solter and Knowles 1978;Fox et al 1981;Kannagi et al 1982;Knowles et al 1982;Lagenaur et al 1982;Liebert et al 1987;Sekine et al 1987;Son et al 2009 SSEA-2 4 -8-cell embryo blastomeres mouse spermatozoa Shevinsky et al 1981 SSEA-3 Galb1-3GalNAcb1-3Gala1-4 Galb1-4 Glc ceramide Damjanov et al 1982;Jessell and Dodd 1985;Sekine et al 1987;Ohyama et al 1995;Thomson et al 1998;Chang et al 2008 SSEA-4 NeuAca2-3Galb1-3GalNAcb1-3Gala1-4 Galb1-4 Glc ceramide Pleuripotent embryonic stem cells, dorsal root ganglia, kidney, renal carcinoma, testicular germ cell tumors Holford et al 1994;Cooling et al 1995;Thomson et al 1998;Saito et al 2003;Gang et al 2007 sialidase deficiency but rather b-hexosaminidase. Hexosaminidase comprises one a and one b subunit.…”