Publications by authors named "Sumeyye Cavdarli"

6 Publications

  • Page 1 of 1

-acetylated Gangliosides as Targets for Cancer Immunotherapy.

Cells 2020 03 17;9(3). Epub 2020 Mar 17.

UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, CNRS, Université de Lille, F-59000 Lille, France.

-acetylation of sialic acid residues is one of the main modifications of gangliosides, and modulates ganglioside functions. -acetylation of gangliosides is dependent on sialyl--acetyltransferases and sialyl--acetyl-esterase activities. CAS1 Domain-Containing Protein 1 (CASD1) is the only human sialyl--acetyltransferases (SOAT) described until now. -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 -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 -acetylation analysis and expression in cancers, and of the possible use of -acetylated gangliosides as targets for cancer immunotherapy.
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http://dx.doi.org/10.3390/cells9030741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140702PMC
March 2020

Glycosylation changes in inflammatory diseases.

Adv Protein Chem Struct Biol 2020 26;119:111-156. Epub 2019 Nov 26.

University Lille, CNRS, UMR 8576 - UGSF - Unite de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France.

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 a number of inflammatory diseases. Pro-inflammatory cytokines have been shown to modulate cell surface glycosylation by regulating the expression of glycosyltransferases and sulfotransferases involved in the biosynthesis of glycan chains, inducing the expression of specific carbohydrate antigens at the cell surface that can be recognized by different types of lectins or by bacterial adhesins, contributing to the development of diseases. Glycosylation can also regulate biological functions of immune cells by recruiting leukocytes to inflammation sites with pro- or anti-inflammatory effects. Cell surface proteoglycans provide a large panel of binding sites for many mediators of inflammation, and regulate their bio-availability and functions. In this review, we summarize the current knowledge of the glycosylation changes occurring in mucin type O-linked glycans, glycosaminoglycans, as well as in glycosphingolipids, with a particular focus on cystic fibrosis and neurodegenerative diseases, and their consequences on cell interactions and disease progression.
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http://dx.doi.org/10.1016/bs.apcsb.2019.08.008DOI Listing
January 2021

Profiling of -acetylated Gangliosides Expressed in Neuroectoderm Derived Cells.

Int J Mol Sci 2020 Jan 6;21(1). Epub 2020 Jan 6.

Univ. Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France.

The expression and biological functions of oncofetal markers GD2 and GD3 were extensively studied in neuroectoderm-derived cancers in order to characterize their potential as therapeutic targets. Using immunological approaches, we previously identified GD3, GD2, and AcGD2 expression in breast cancer (BC) cell lines. However, antibodies specific for -acetylated gangliosides are not exempt of limitations, as they only provide information on the expression of a limited set of -acetylated ganglioside species. Consequently, the aim of the present study was to use structural approaches in order to apprehend ganglioside diversity in melanoma, neuroblastoma, and breast cancer cells, focusing on -acetylated species that are usually lost under alkaline conditions and require specific analytical procedures. We used purification and extraction methods that preserve the -acetyl modification for the analysis of native gangliosides by MALDI-TOF. We identified the expression of GM1, GM2, GM3, GD2, GD3, GT2, and GT3 in SK-Mel28 (melanoma), LAN-1 (neuroblastoma), Hs 578T, SUM 159PT, MDA-MB-231, MCF-7 (BC), and BC cell lines over-expressing GD3 synthase. Among -acetylated gangliosides, we characterized the expression of AcGM1, AcGD3, AcGD2, AcGT2, and AcGT3. Furthermore, the experimental procedure allowed us to clearly identify the position of the sialic acid residue that carries the -acetyl group on b- and c-series gangliosides by MS/MS fragmentation. These results show that ganglioside -acetylation occurs on both inner and terminal sialic acid residue in a cell type-dependent manner, suggesting different -acetylation pathways for gangliosides. They also highlight the limitation of immuno-detection for the complete identification of -acetylated ganglioside profiles in cancer cells.
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http://dx.doi.org/10.3390/ijms21010370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981417PMC
January 2020

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

Biomolecules 2019 07 27;9(8). Epub 2019 Jul 27.

Université de Lille, CNRS, UMR8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, F59000 Lille, France.

Gangliosides, the glycosphingolipids carrying one or several sialic acid residues, are mostly localized at the plasma membrane in lipid raft domains and implicated in many cellular signaling pathways mostly by interacting with tyrosine kinase receptors. Gangliosides are divided into four series according to the number of sialic acid residues, which can be also modified by -acetylation. Both ganglioside expression and sialic acid modifications can be modified in pathological conditions such as cancer, which can induce either pro-cancerous or anti-cancerous effects. In this review, we summarize the specific functions of gangliosides in neuro-ectodermal derived tumors, and their roles in reprogramming the lipidomic profile of cell membrane occurring with the induction of epithelial-mesenchymal transition.
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http://dx.doi.org/10.3390/biom9080311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723632PMC
July 2019

Identification of 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac) as main O-acetylated sialic acid species of GD2 in breast cancer cells.

Glycoconj J 2019 02 5;36(1):79-90. Epub 2019 Jan 5.

CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, University Lille, F-59000, Lille, France.

Mainly restricted to the nervous system in healthy adults, complex gangliosides such as GD3 and GD2 have been shown to be involved in aggressiveness and metastasis of neuro-ectoderm derived tumors such as melanoma and neuroblastoma. Interestingly, O-acetylated forms of GD2, not expressed in human peripheral nerve fibers, are highly expressed in GD2+ tumor cells. Very little information is known regarding the expression of O-acetylated disialogangliosides in breast cancer (BC) cell lines. Here, we analyzed the expression of GD2, GD3 and their O-acetylated forms O-acetyl-GD2 (OAcGD2) and O-acetyl-GD3 (OAcGD3) in BC cells. We used Hs 578T and SUM159PT cell lines, as well as cell clones over-expressing GD3 synthase derived from MDA-MB-231 and MCF-7. Using flow cytometry and immunocytochemistry/confocal microscopy, we report that BC cells express b-series gangliosides GD3 and GD2, as well as significant amounts of OAcGD2. However, OAcGD3 expression was not detected in these cells. O-acetylation of gangliosides isolated from BC cells was examined by LC-MS analysis of sialic acid DMB-derivatives. We report that the main acetylated form of sialic acid expressed in BC gangliosides is 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac). These results highlight a close interrelationship between Neu5,9Ac and OAcGD2 expression, and suggest that OAcGD2 is synthetized from GD2 and not from OAcGD3 in BC cells.
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http://dx.doi.org/10.1007/s10719-018-09856-wDOI Listing
February 2019

TNF differentially regulates ganglioside biosynthesis and expression in breast cancer cell lines.

PLoS One 2018 26;13(4):e0196369. Epub 2018 Apr 26.

University of Lille, Structural and Functional Glycobiology Unit, UMR CNRS 8576, Lille, France.

Gangliosides are glycosphingolipids concentrated in glycolipid-enriched membrane microdomains. Mainly restricted to the nervous system in healthy adult, complex gangliosides such as GD3 and GD2 have been shown to be involved in aggressiveness and metastasis of neuro-ectoderm derived tumors such as melanoma and neuroblastoma. GD3 synthase (GD3S), the key enzyme that controls the biosynthesis of complex gangliosides, was shown to be over-expressed in Estrogen Receptor (ER)-negative breast cancer tumors, and associated with a decreased overall survival of patients. We previously demonstrated that GD3S expression in ER-negative breast cancer cells induced a proliferative phenotype and an increased tumor growth. In addition, our results clearly indicate that Tumor Necrosis Factor (TNF) induced GD3S over-expression in breast cancer cells via NFκB pathway. In this study, we analyzed the effect of TNF on ganglioside biosynthesis and expression in breast cancer cells from different molecular subtypes. We showed that TNF up-regulated the expression of GD3S in MCF-7 and Hs578T cells, whereas no change was observed for MDA-MB-231. We also showed that TNF induced an increased expression of complex gangliosides at the cell surface of a small proportion of MCF-7 cells. These results demonstrate that TNF differentially regulates gangliosides expression in breast cancer cell lines and establish a possible link between inflammation at the tumor site environment, expression of complex gangliosides and tumor development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196369PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919650PMC
August 2018