Gangliosides: The Double-Edge Sword of Neuro-Ectodermal Derived Tumors

Cavdarli, Sumeyye; Groux-Degroote, Sophie; Delannoy, Philippe

doi:10.3390/biom9080311

Cited by 57 publications

(71 citation statements)

References 93 publications

(123 reference statements)

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“…We have previously demonstrated that ganglioside-containing exosomes, as well as vesicles prepared from extracted exosome lipids and ganglioside-containing model mixtures, accelerate the amyloid formation of α-synuclein, which is related to Parkinson's disease [8]. Ganglioside lipids have also been proposed to be relevant for other diseases, for example, Alzheimer's disease, Tay-Sachs disease, and cancer [9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Self-Assembly in Ganglioside‒Phospholipid Systems: The Co-Existence of Vesicles, Micelles, and Discs

Mojumdar

Grey

Sparr

2019

IJMS

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Ganglioside lipids have been associated with several physiological processes, including cell signaling. They have also been associated with amyloid aggregation in Parkinson’s and Alzheimer’s disease. In biological systems, gangliosides are present in a mix with other lipid species, and the structure and properties of these mixtures strongly depend on the proportions of the different components. Here, we study self-assembly in model mixtures composed of ganglioside GM1 and a zwitterionic phospholipid, 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC). We characterize the structure and molecular dynamics using a range of complementary techniques, including cryo-TEM, polarization transfer solid state NMR, diffusion NMR, small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and calorimetry. The main findings are: (1) The lipid acyl chains are more rigid in mixtures containing both lipid species compared to systems that only contain one of the lipids. (2) The system containing DOPC with 10 mol % GM1 contains both vesicles and micelles. (3) At higher GM1 concentrations, the sample is more heterogenous and also contains small disc-like or rod-like structures. Such a co-existence of structures can have a strong impact on the overall properties of the lipid system, including transport, solubilization, and partitioning, which can be crucial to the understanding of the role of gangliosides in biological systems.

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Section: Introductionmentioning

confidence: 99%

Self-Assembly in Ganglioside‒Phospholipid Systems: The Co-Existence of Vesicles, Micelles, and Discs

Mojumdar

Grey

Sparr

2019

IJMS

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“…MS/MS fragmentation of these O-acetylated gangliosides species showed that O-acetylation can occur both on the terminal and on the subterminal sialic acid of the ganglioside carbohydrate moiety [51]. To get further insight into the position of the O-acetyl group on the sialic acid residue, DMB-labeled sialic acid derivatives extracted from gangliosides from BC cells were analyzed by LC-ES-MS. 9-O-acetyl-N-acetyl-neuraminic acid was identified as the main O-acetylated sialic acid species expressed on gangliosides from BC cells [4,51].…”

Section: Analysis Of O-acetylated and Non-o-acetylated Gangliosides Smentioning

confidence: 96%

“…Within lipid rafts, gangliosides play an active role in regulating receptor tyrosine kinases and cell signaling pathways involved in a large number of biological processes including vesicular traffic, cell polarity, or cell proliferation [2,3]. Changes in ganglioside composition are observed in many cancers, especially from a neuroectoderm origin, which exhibit aberrant ganglioside profiles, and several ganglioside species are considered as tumor-associated carbohydrate antigens, usually associated with a poor prognosis of the patient [4]. Sialic acid residues can be also O-acetylated, increasing the structural heterogeneity of the oligosaccharide structures and modulating ganglioside functions.…”

Section: Introductionmentioning

confidence: 99%

O-acetylated Gangliosides as Targets for Cancer Immunotherapy

Cavdarli

Delannoy

Groux-Degroote

2020

Cells

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O-acetylation of sialic acid residues is one of the main modifications of gangliosides, and modulates ganglioside functions.O-acetylation of gangliosides is dependent on sialyl-O-acetyltransferases and sialyl-O-acetyl-esterase activities. CAS1 Domain-Containing Protein 1 (CASD1) is the only human sialyl-O-acetyltransferases (SOAT) described until now. O-acetylated ganglioside species are mainly expressed during embryonic development and in the central nervous system in healthy adults, but are re-expressed during cancer development and are considered as markers of cancers of neuroectodermal origin. However, the specific biological roles of O-acetylated gangliosides in developing and malignant tissues have not been extensively studied, mostly because of the requirement of specific approaches and tools for sample preparation and analysis. In this review, we summarize our current knowledge of ganglioside biosynthesis and expression in normal and pathological conditions, of ganglioside O-acetylation analysis and expression in cancers, and of the possible use of O-acetylated gangliosides as targets for cancer immunotherapy. a potential functional significance of ganglioside O-acetylation in cancer. The use of O-acetylated gangliosides as targets for cancer immunotherapy is also discussed. Ganglioside Structures and BiosynthesisGangliosides are acidic GSL containing from one to five sialic acids residues. They are mainly, but not exclusively, derived from ganglio-series GSL (GgCer) that result from the substitution of a ceramide (Cer) by the tetrasaccharide core Galβ1-3GalNAcβ1-4Galβ1-4Glcβ (Gg4). In different cell types and tissues, gangliosides are usually found as a mixture of di-, tri-and tetrasaccharide cores substituted by one or more sialic acid residues [1,5]. The biosynthesis of gangliosides takes place in the Golgi apparatus and starts by the transfer of sialic acid residues to lactosylceramide (LacCer) by specific sialyltransferases, i.e., the CMP-Neu5Ac: LacCer α2,3-sialyltransferase ST3Gal V (GM3 synthase) [6], the CMP-Neu5Ac: GM3 α2,8-sialyltransferase ST8Sia I (GD3 synthase) [7] and the CMP-Neu5Ac: GD3 α2,8-sialyltransferase ST8Sia V [8], that show high specificity toward glycolipid substrates [9]. Thus, LacCer, GM3, GD3 and GT3 are the precursors for 0-, a-, b-and c-series gangliosides, respectively (Figure 1).

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“…Gangliosides such as GM3, GM2, GM1, and GD1 are expressed across many normal human tissues ( 6 , 10 – 12 ) and appear to have multiple biological functions, particularly cell recognition and regulation of membrane-bound signaling proteins such as epidermal growth factor receptor and vascular endothelial growth factor receptor ( 10 , 13 ). In contrast, expression of disialoganglioside GD2 in normal tissues is limited essentially to the central nervous system, peripheral sensory nerve fibers, dermal melanocytes, lymphocytes, and mesenchymal stem cells ( 12 , 14 , 15 ). Although disialoganglioside GD2 appears to participate in cell signaling, its function in normal cellular physiology has not been fully elucidated and therefore is not well-understood ( 16 ).…”

Section: Introductionmentioning

confidence: 99%