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Molecules 2012, 17(8), 9559-9572; doi:10.3390/molecules17089559
Article

Accumulation of Unusual Gangliosides GQ3 and GP3 in Breast Cancer Cells Expressing the GD3 Synthase

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Received: 18 June 2012; in revised form: 20 July 2012 / Accepted: 6 August 2012 / Published: 10 August 2012
(This article belongs to the Special Issue Advances in Carbohydrate Chemistry)
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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 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 gangliosides; GD3 synthase; MCF-7; unusual gangliosides
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.



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