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Role of tumour-associated N-glycolylated variant of GM3 ganglioside in cancer progression: effect over CD4 expression on T cells

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Abstract

Gangliosides have diverse biological functions including modulation of immune system response. These molecules are differentially expressed on malignant cells compared with the corresponding normal ones and are involved in cancer progression affecting, in different ways, the host’s anti-tumour specific immune responses. Although in humans the N-glycolylated variant of GM3 ganglioside is almost exclusively expressed in tumour tissues, the significance of this glycolipid for malignant cell biology remains obscure, while for NAcGM3 strong immune suppressive effects have been reported. The present work demonstrates, for the first time, the capacity of NGcGM3 ganglioside to down-modulate CD4 expression in murine and human T lymphocytes, especially in non-activated T cells. Thirty and tenfold reductions in CD4 expression were induced by purified NGcGM3 ganglioside in murine and human T lymphocytes, respectively. The CD4 complete recovery in these cells occurred after 48 h of ganglioside removal, due to neo-synthesis. Restored T cells kept similar sensitivity to ganglioside-induced CD4 down-modulation after a new challenge. In addition, a clear association between NGcGM3 insertion in lymphocyte plasma membranes and the CD4 down-modulation effect was documented. Notably, a possible role of this ganglioside in tumour progression, taking advantage of the X63 myeloma model, was also outlined. The relevance of these findings, characterizing NGcGM3 as a possible tumour immunesurveillance inhibitor and supporting the reason for its neo-expression in certain human cancers, is contributing to this unique heterophilic ganglioside validation as target for cancer immunotherapy.

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Abbreviations

CMP-NeuAc:

Monophosphoril citidin N-acetyl sialic acid

D-PDMP:

D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol

NAcGM3:

N-acetylated GM3

NGcGM3:

N-glycolylated GM3

NGNA:

N-glycolylneuraminic acid

TFI:

Total fluorescent intensity

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Acknowledgements

We thank Armando Lopez for excellent technical assistance and Dr Blanca Tormo for skilful manuscript edition. This work was supported by the Centre of Molecular Immunology (Havana, Cuba).

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Authors and Affiliations

  1. Vaccine Department, Centre of Molecular Immunology, 216 esq 15, Atabey, Playa, 16040, C. Habana, Cuba

    Joel de Leòn, Audry Fernández, Circe Mesa, Marilyn Clavel & Luis E. Fernández

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  1. Joel de Leòn
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  2. Audry Fernández
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  3. Circe Mesa
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  5. Luis E. Fernández
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Correspondence to Joel de Leòn.

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Leòn, J.d., Fernández, A., Mesa, C. et al. Role of tumour-associated N-glycolylated variant of GM3 ganglioside in cancer progression: effect over CD4 expression on T cells. Cancer Immunol Immunother 55, 443–450 (2006). https://doi.org/10.1007/s00262-005-0041-6

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