Gangliosides in breast cancer: New perspectives

Groux-Degroote, Sophie; Guérardel, Yann; Julien, Sylvain; Delannoy, Philippe

doi:10.1134/s0006297915070020

Cited by 21 publications

(8 citation statements)

References 96 publications

(98 reference statements)

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“…Gangliosides are sialic acid bearing glycosphingolipids expressed on all vertebrate cell membranes [ 15 ] and are anchored to the plasma membrane through ceramide lipids. Among gangliosides, GD2 is known to be highly expressed in ectoderm origin tumors such as neuroblastoma, melanoma, T-cell leukemia [ 16 – 18 ] and breast cancer stem cells [ 19 ] whereas they are weakly expressed in their normal tissues [ 20 , 21 ]. Therefore, GD2 is considered to be a cancer-associated antigen.…”

Section: Introductionmentioning

confidence: 99%

Expression of ganglioside GD2, reprogram the lipid metabolism and EMT phenotype in bladder cancer

et al. 2017

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High-grade Bladder Cancer (BLCA) represents the most aggressive and treatment-resistant cancer that renders the patients with poor survival. However, only a few biomarkers have been identified for the detection and treatment of BLCA. Recent studies show that ganglioside GD2 can be used as cancer biomarker and/or therapeutic target for various cancers. Despite its potential relevance in cancer diagnosis and therapeutics, the role of GD2 is unknown in BLCA. Here, we report for the first time that high-grade BLCA tissues and cell lines have higher expression of GD2 compared to low-grade by high-resolution Mass Spectrometry. The muscle invasive UMUC3 cell line showed high GD2, mesenchymal phenotype, and cell proliferation. Besides, we have shown the cancer stem cells (CSC) property (CD44hiCD24lo) of GD2+ UMUC3 and J82 cells. Also, the evaluation of lipid metabolism in GD2+ BLCA cell lines revealed higher levels of Phosphatidylinositol (PI), Phosphatidic acid (PA), Cardiolipin (CL) and lower levels of Phosphatidylserine (PS), plasmenyl-phosphatidylethanolamines (pPE), plasmenyl-phosphocholines (pPC), sphingomyelins (SM), triglycerides (TGs) and N-Acetylneuraminic acid. These findings are significantly correlated with the tissues of BLCA patients. Based on this evidence, we propose that GD2 may be used as an effective diagnostic and therapeutic target for aggressive BLCA.

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Section: Introductionmentioning

confidence: 99%

Expression of ganglioside GD2, reprogram the lipid metabolism and EMT phenotype in bladder cancer

et al. 2017

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“…It is well known that gangliosides such as G D3 and G D2 are oncofetal markers in neuro-ectoderm derived cancer including melanoma, neuroblastoma and breast cancer, where they play a key role in tumor progression [72,96]. In this context, the modulation of ganglioside expression by pro-inflammatory cytokines is of growing interest.…”

Section: Regulation Of Ganglioside Expression By Pro-inflammatory mentioning

confidence: 99%

Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer

Dewald

Colomb

Bobowski-Gerard

et al. 2016

Cells

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Glycosylation is one of the most important modifications of proteins and lipids, and cell surface glycoconjugates are thought to play important roles in a variety of biological functions including cell-cell and cell-substrate interactions, bacterial adhesion, cell immunogenicity and cell signaling. Alterations of glycosylation are observed in number of diseases such as cancer and chronic inflammation. In that context, pro-inflammatory cytokines have been shown to modulate cell surface glycosylation by regulating the expression of glycosyltransferases involved in the biosynthesis of carbohydrate chains. These changes in cell surface glycosylation are also known to regulate cell signaling and could contribute to disease pathogenesis. This review summarizes our current knowledge of the glycosylation changes induced by pro-inflammatory cytokines, with a particular focus on cancer and cystic fibrosis, and their consequences on cell interactions and signaling.

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“…GD3 and/or GD2 are frequently expressed in ectoderm-derived tumors (e.g. neuroblastoma, melanoma, T-cell leukemia, breast cancer) in adults, and are therefore considered to be cancer-associated antigens [ 7 – 9 ]. GD3, GD2, and certain other gangliosides are thought of as promising targets for cancer immunotherapy because their expression is restricted to malignant cells and they are accessible on the cell surface.…”

Section: Introductionmentioning

confidence: 99%

Interaction of glycosphingolipids GD3 and GD2 with growth factor receptors maintains breast cancer stem cell phenotype

Liang

Wang

et al. 2017

Oncotarget

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Many studies have suggested that disialogangliosides, GD2 and GD3, are involved in the development of various tumor types. However, the functional relationships between ganglioside expression and cancer development or aggressiveness are not fully described. GD3 is upregulated in approximately half of all invasive ductal breast carcinoma cases, and enhanced expression of GD3 synthase (GD3S, alpha-N-acetylneuraminide alpha-2,8-sialyltransferase) in estrogen receptor-negative breast tumors, was shown to correlate with reduced overall patient survival. We previously found that GD2 and GD3, together with their common upstream glycosyltransferases, GD3S and GD2/GM2 synthase, maintain a stem cell phenotype in breast cancer stem cells (CSCs). In the current study, we demonstrate that GD3S alone can sustain CSC properties and also promote malignant cancer properties. Using MALDI-MS and flow cytometry, we found that breast cancer cell lines, of various subtypes with or without ectopic GD3S-expression, exhibited distinct GD2/GD3 expression profiles. Furthermore, we found that GD3 was associated with EGFR and activated EGFR signaling in both breast CSCs and breast cancer cell lines. In addition, GD3S knockdown enhanced cytotoxicity of the EGFR-inhibitor gefitinib in resistant MDA-MB468 cells, both in vitro and in vivo. Based on this evidence, we propose that GD3S contributes to gefitinib-resistance in EGFR-positive breast cancer cells and may be an effective therapeutic target in drug-resistant breast cancers.

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Gangliosides in breast cancer: New perspectives

Cited by 21 publications

References 96 publications

Expression of ganglioside GD2, reprogram the lipid metabolism and EMT phenotype in bladder cancer

Expression of ganglioside GD2, reprogram the lipid metabolism and EMT phenotype in bladder cancer

Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer

Interaction of glycosphingolipids GD3 and GD2 with growth factor receptors maintains breast cancer stem cell phenotype

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