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Induction of GM1a/GD1b synthase triggers complex ganglioside expression and alters neuroblastoma cell behavior; a new tumor cell model of ganglioside function

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Abstract

Neuroblastoma is the most common extracranial solid tumor in children and tumor ganglioside composition has been linked to its biological and clinical behavior. We recently found that high expression of complex gangliosides that are products of the enzyme GM1a/GD1b synthase predicts a more favorable outcome in human neuroblastoma, and others have shown that complex gangliosides such as GD1a inhibit metastasis of murine tumors. To determine how a switch from structurally simple to structurally complex ganglioside expression affects neuroblastoma cell behavior, we engineered IMR32 human neuroblastoma cells, which contain almost exclusively (89%) the simple gangliosides (SG) GM2, GD2, GM3, and GD3, to overexpress the complex gangliosides (CG) GM1, GD1a, GD1b and GT1b, by stable retroviral-mediated transduction of the cDNA encoding GM1a/GD1b synthase. This strikingly altered cellular ganglioside composition without affecting total ganglioside content: There was a 23-fold increase in the ratio of complex to simple gangliosides in GM1a/GD1b synthase-transduced cells (IMR32-CG) vs. wild type (IMR32) or vector-transfected (IMR32-V) cells with essentially no expression of the clinical neuroblastoma marker, GD2, confirming effectiveness of this molecular switch from simple to complex ganglioside synthesis. Probing for consequences of the switch, we found that among functional properties of IMR32-CG cells, cell migration was inhibited and Rho/Rac1 activities were altered, while proliferation kinetics and cell differentiation were unaffected. These findings further implicate cellular ganglioside composition in determining cell migration characteristics of tumor cells. This IMR32 model system should be useful in delineating the impact of ganglioside composition on tumor cell function.

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Acknowledgements

We are grateful to Su Yan, Liangping Yuan, and Michael Weiss for their assistance in this work. This work was supported by National Institutes of Health grants R01 CA 61010 (S.L.) and R01 CA106532 (K.K., S.L.).

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Authors and Affiliations

  1. Center for Cancer and Immunology Research, Children’s National Medical Center, 111 Michigan Avenue, NW, Washington, DC, 20010, USA

    Lixian Dong, Yihui Liu, Anamaris M. Colberg-Poley, Karen Kaucic & Stephan Ladisch

  2. Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Lixian Dong, Yihui Liu & Karen Kaucic

  3. Departments of Pediatrics and of Biochemistry and Molecular Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Anamaris M. Colberg-Poley & Stephan Ladisch

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  1. Lixian Dong
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Correspondence to Stephan Ladisch.

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Dong, L., Liu, Y., Colberg-Poley, A.M. et al. Induction of GM1a/GD1b synthase triggers complex ganglioside expression and alters neuroblastoma cell behavior; a new tumor cell model of ganglioside function. Glycoconj J 28, 137–147 (2011). https://doi.org/10.1007/s10719-011-9330-9

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