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Accumulation of Unusual Gangliosides GQ3 and GP3 in Breast Cancer Cells Expressing the GD3 Synthase
Structural and Functional Glycobiology Unit, UMR CNRS 8576, University of Sciences and Technologies of Lille, 59655 Villeneuve d’Ascq, France
INSERM U908, University of Sciences and Technologies of Lille, 59655 Villeneuve d’Ascq, France
These authors contributed equally to this work.
Current address: Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
Current address: Department of Rheumatology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
* Author to whom correspondence should be addressed.
Received: 18 June 2012; in revised form: 20 July 2012 / Accepted: 6 August 2012 / Published: 10 August 2012
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 18.104.22.168, 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 GM3, GM2, and GM1a. 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 GQ3 (II3Neu5Ac4-Gg2Cer) and GP3 (II3Neu5Ac5-Gg2Cer). This indicates that ST8Sia I is able to act as an oligosialyltransferase in a cellular context.
Keywords: gangliosides; GD3 synthase; MCF-7; unusual gangliosides
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Steenackers, A.; Vanbeselaere, J.; Cazet, A.; Bobowski, M.; Rombouts, Y.; Colomb, F.; Bourhis, X.L.; Guérardel, Y.; Delannoy, P. Accumulation of Unusual Gangliosides GQ3 and GP3 in Breast Cancer Cells Expressing the GD3 Synthase. Molecules 2012, 17, 9559-9572.
Steenackers A, Vanbeselaere J, Cazet A, Bobowski M, Rombouts Y, Colomb F, Bourhis XL, Guérardel Y, Delannoy P. Accumulation of Unusual Gangliosides GQ3 and GP3 in Breast Cancer Cells Expressing the GD3 Synthase. Molecules. 2012; 17(8):9559-9572.
Steenackers, Agata; Vanbeselaere, Jorick; Cazet, Aurélie; Bobowski, Marie; Rombouts, Yoann; Colomb, Florent; Bourhis, Xuefen Le; Guérardel, Yann; Delannoy, Philippe. 2012. "Accumulation of Unusual Gangliosides GQ3 and GP3 in Breast Cancer Cells Expressing the GD3 Synthase." Molecules 17, no. 8: 9559-9572.