Accumulation of unusual gangliosides G(Q3) and G(P3) in breast cancer cells expressing the G(D3) synthase.

Abstract

Glycosphingolipids from the ganglio-series are usually classified in four series according to the presence of 0 to 3 sialic acid residues linked to lactosylceramide. The transfer of sialic acid is catalyzed in the Golgi apparatus by specific sialyltransferases that show high specificity toward glycolipid substrates. ST8Sia I (EC 2.4.99.8, SAT-II, SIAT 8a) is the key enzyme controlling the biosynthesis of b- and c-series gangliosides. ST8Sia I is expressed at early developmental stages whereas in adult human tissues, ST8Sia I transcripts are essentially detected in brain. ST8Sia I together with b- and c-series gangliosides are also over-expressed in neuroectoderm-derived malignant tumors such as melanoma, glioblastoma, neuroblastoma and in estrogen receptor (ER) negative breast cancer, where they play a role in cell proliferation, migration, adhesion and angiogenesis. We have stably expressed ST8Sia I in MCF-7 breast cancer cells and analyzed the glycosphingolipid composition of wild type (WT) and GD3S+ clones. As shown by mass spectrometry, MCF-7 expressed a complex pattern of neutral and sialylated glycosphingolipids from globo- and ganglio-series. WT MCF-7 cells exhibited classical monosialylated gangliosides including G(M3), G(M2), and G(M1a). In parallel, the expression of ST8Sia I in MCF-7 GD3S+ clones resulted in a dramatic change in ganglioside composition, with the expression of b- and c-series gangliosides as well as unusual tetra- and pentasialylated lactosylceramide derivatives G(Q3) (II(3)Neu5Ac(4)-Gg(2)Cer) and G(P3) (II(3)Neu5Ac(5)-Gg(2)Cer). This indicates that ST8Sia I is able to act as an oligosialyltransferase in a cellular context.

• Authors: Agata Steenackers, Jorick Vanbeselaere, Aurélie Cazet, Marie Bobowski, Yoann Rombouts, Florent Colomb, Xuefen Le Bourhis, Yann Guérardel, Philippe Delannoy
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 17 Issue 8 Pg. 9559-72 (Aug 10 2012) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 22885356 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gangliosides
• Glycosphingolipids
• Sialyltransferases
• alpha-N-acetylneuraminate alpha-2,8-sialyltransferase

Topics

• Breast Neoplasms (genetics, metabolism)
• Female
• Gangliosides (biosynthesis, metabolism)
• Gene Expression
• Glycosphingolipids (metabolism)
• Humans
• MCF-7 Cells
• Methylation
• Sialyltransferases (genetics, metabolism)