Papers by Philippe Delannoy
Glycobiology, Jun 1, 2000
Permanent exposure of differentiated HT-29 cells to the sugar analogue, 1-benzyl-2-acetamido-2-de... more Permanent exposure of differentiated HT-29 cells to the sugar analogue, 1-benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (GalNAcα-O-bn) leads to marked effects upon the phenotypic properties of mucin-secreting or enterocytelike HT-29 cells: an inhibition in the secretion of mucins, a blockade in the apical targeting of membrane brush border glycoproteins and a swelling of cells with intracellular accumulation of numerous vesicles. Folch extraction and partition of treated enterocyte-like HT-29 cells revealed a very important accumulation of orcinol and/or resorcinol reactive material in the upper phase (usually containing gangliosides), as compared with untreated HT-29 cells and with treated and untreated Caco-2 cells. Structural analysis indicated the accumulation of a series of GalNAcα-O-bn derived oligosaccharides, most of them with the common core Galβ1-3GalNAcα-O-bn. These oligosaccharides contained residues of GlcNAc, Gal, Neu5Ac, or Fuc. In particular, the tagged sialyl-Lewis x was identified, as well as more complex sialylated derivatives, including the sialyl-Lewis x substituted by an additional Neu5Ac residue. The benzylated oligosaccharides were not significantly detected in the culture medium except for Galβ1-3GalNAcα-O-bn. Upon reversion of the treatment, these derivatives disappeared from the cells within few days, however were not recovered as such in the culture medium. Intracellular degradation occurred with desialylation and defucosylation as the first steps. The spectacular accumulation of benzylated oligosaccharides in HT-29 cell, permanently exposed to GalNAcα-O-bn very likely plays an important role in the alterations of cellular processes previously described in this cell line. The HT-29 cell culture system also appears to be an efficient source of several tagged oligosaccharides.
Journal of Cell Biology, Jun 15, 1998
Exposure for 24 h of mucus-secreting HT-29 cells to the sugar analogue GalNAc-␣ -O -benzyl result... more Exposure for 24 h of mucus-secreting HT-29 cells to the sugar analogue GalNAc-␣ -O -benzyl results in inhibition of Gal  1-3GalNAc: ␣ 2,3-sialyltransferase, reduced mucin sialylation, and inhibition of their secretion (Huet, G., I.
Frontiers in Bioscience, 2001
PubMed, Sep 15, 1998
Increased sialylation, especially involving the Sialyl-Lewisa and Sialyl-Lewisx determinants, has... more Increased sialylation, especially involving the Sialyl-Lewisa and Sialyl-Lewisx determinants, has been reported in breast cancer. A multiplex reverse transcription-PCR method was used here to determine the expression of five sialyltransferases (ST3Gal III, ST6Gal I, ST3Gal IV, ST3Gal I, and ST3Gal II) in 49 patients surgically treated for locoregional breast cancer. We assessed the relationship between these expressions and clinical, pathological, and biological features. The most expressed sialyltransferase was ST3Gal 1II, which is involved in Sialyl-Lewisa synthesis. ST3Gal III expression was positively correlated to ST6Gal I and ST3Gal IV expressions, to tumor size, and to the number of involved axillary nodes. Patients with high ST3Gal III expression had a shorter overall survival. High ST6Gal I expression was associated with histoprognostic grade III. ST6Gal I expression was negatively correlated to expression of progesterone receptor. In conclusion, high ST3Gal III and ST6Gal I expressions in human breast tumors are associated with poor prognosis markers.
HAL (Le Centre pour la Communication Scientifique Directe), Jun 2, 2013
The CMP-sialic acid: sialylα2-3Galβ1-4Glcβ1-O-Cer α2,8-sialyltransferase (ST8Sia I) is the key en... more The CMP-sialic acid: sialylα2-3Galβ1-4Glcβ1-O-Cer α2,8-sialyltransferase (ST8Sia I) is the key enzyme for the biosynthesis of b-series gangliosides. ST8Sia I catalyses the transfer of a sialic acid residue from CMP-sialic acid onto GM3 (Neu5Acα2-3Galβ1-4Glcβ1-O-Cer) to form GD3 (Neu5Acα2-8Neu5Acα2-3Galβ1-4Glcβ1-O-Cer). The product GD3 can be converted in GT3, and both compounds can be elongated by other monosaccharides (i.e. GalNAc, Gal and sialic acid) to form the b- and c-series gangliosides. Gangliosides from b- and c-series are essentially found in developing tissues during embryogenesis, and mainly restricted to the nervous system in healthy adults. They are enriched in glycolipid-enriched microdomains where they play a key role in the modulation of signal transduction. Moreover, substantial evidences have demonstrated the implication of ST8Sia I and b- and c-series gangliosides in oncogenesis by mediating cell proliferation, migration, tumor growth and angiogenesis.
M S-medecine Sciences, Jun 1, 2021
médecine/sciences Les mécanismes de régulation de la glycosylation Exemples d'altérations des cha... more médecine/sciences Les mécanismes de régulation de la glycosylation Exemples d'altérations des chaînes glycanniques dans les cancers
Royal Society of Chemistry eBooks, Apr 29, 2015
Carbohydrate Chemistry, 2021
Inflammatory Disorders, Part A, 2019
Glycosylation is one of the most important modifications of proteins and lipids, and cell surface... more 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.
Recent Advances in Biotechnology, 2016
Topics in Current Chemistry, 2015
Sialic Acid Receptors of Viruses.- Endosialidases- versatile tools for the study of polysialic ac... more Sialic Acid Receptors of Viruses.- Endosialidases- versatile tools for the study of polysialic acid.- Advanced technologies in sialic acid and sialoglycoconjugate analysis.- Development and applications of the lectin microarray.- Sialoside Arrays: New Synthetic Strategies and Applications.- SIGLEC4 Antagonists.- Chemical Approach to A Whole Body Imaging of Sialo-N-linked Glycans.- Trypanosomal Trans-sialidases: Valuable Synthetic Tools and Targets for Medicinal Chemistry.
Carbohydrate Chemistry
ABSTRACT Mucins are high molecular weight glycoproteins characterized by highly O-glycosylated ta... more ABSTRACT Mucins are high molecular weight glycoproteins characterized by highly O-glycosylated tandem repeat domains. Mucin-type O-glycans exhibit a variety of terminal sequences including histo-blood group antigens that serve as counter receptors and participate in the adhesion and clearance of numerous bacteria including pathogens. In parallel, the pathological changes of mucin glycosylation modulate bacterial adhesion, often enhancing the adhesion of pathogenic bacteria. This review summarizes the current knowledge on the structure and biosynthesis of epithelial mucin O-glycans chains, the physio-pathological glycosylation repertoire of mucins and the role of mucin glycosyla- tion in bacterial adhesion, focusing on the gastrointestinal tract and airway mucins.
Oncology Reports, 2007
1-O-octadecyl-2-O-methylglycero-3-phosphocholine (ET-18-OMe) treated precultured heart fragments ... more 1-O-octadecyl-2-O-methylglycero-3-phosphocholine (ET-18-OMe) treated precultured heart fragments (PHF) are resistant towards invasion by malignant cells. Previous studies demonstrated that this effect was due to alterations of N-linked glycoproteins in PHF after 48 h ET-18-OMe treatment. Moreover, the observed effect was still present seven days after ET-18-OMe was omitted. The present study reveals that approximately 13.4% of the administered ET-18-OMe was taken up by PHF and about 75% of the initial uptake remained present after ET-18-OMe was removed. In addition, we found significant changes in sialic acid content and sialyltransferase activities in both conditions. Together, these results clearly demonstrate that uptake and retention of ET-18-OMe are responsible for resistance towards invasion of malignant cells due to altered sialylation of cell surface glycoproteins in PHF.
Journal of Cell Science, 2001
Our previous work has shown that long-term treatment of mucus-secreting HT-29 cells with 1-benzyl... more Our previous work has shown that long-term treatment of mucus-secreting HT-29 cells with 1-benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (GalNAcα-O-bn), a competitive inhibitor of O-glycosylation, induced several phenotypic changes, in particular a blockade in the secretion of mucins, which are extensively O-glycosylated glycoproteins. Here, we have analyzed the effects of GalNAcα-O-bn upon the intracellular trafficking of basolateral and apical membrane glycoproteins at the cellular and biochemical levels in two types of cells, HT-29 G− and Caco-2, differentiated into an enterocyte-like phenotype. In HT-29 G− cells, but not in Caco-2 cells, DPP-IV and CD44 failed to be targeted to the apical or basolateral membrane, respectively, and accumulated inside intracytoplasmic vesicles together with GalNAcα-O-bn metabolites. We observed a strong inhibition of α2,3-sialylation of glycoproteins in HT-29 G− cells correlated to the high expression of α2,3-sialyltransferases ST3Gal I and ST3...
PLOS ONE, Mar 9, 2016
Around 7-17% of metastatic breast cancer patients will develop brain metastases, associated with ... more Around 7-17% of metastatic breast cancer patients will develop brain metastases, associated with a poor prognosis. To reach the brain parenchyma, cancer cells need to cross the highly restrictive endothelium of the Blood-Brain Barrier (BBB). As treatments for brain metastases are mostly inefficient, preventing cancer cells to reach the brain could provide a relevant and important strategy. For that purpose an in vitro approach is required to identify cellular and molecular interaction mechanisms between breast cancer cells and BBB endothelium, notably at the early steps of the interaction. However, while numerous studies are performed with in vitro models, the heterogeneity and the quality of BBB models used is a limitation to the extrapolation of the obtained results to in vivo context, showing that the choice of a model that fulfills the biological BBB characteristics is essential. Therefore, we compared pre-established and currently used in vitro models from different origins (bovine, mice, human) in order to define the most appropriate tool to study interactions between breast cancer cells and the BBB. On each model, the BBB properties and the adhesion capacities of breast cancer cell lines were evaluated. As endothelial cells represent the physical restriction site of the BBB, all the models consisted of endothelial cells from animal or human origins. Among these models, only the in vitro BBB model derived from human stem cells both displayed BBB properties and allowed measurement of meaningful different interaction capacities of the cancer cell lines. Importantly, the measured adhesion and transmigration were found to be in accordance with the cancer cell lines molecular subtypes. In addition, at a molecular level, the inhibition of ganglioside biosynthesis highlights the potential role of glycosylation in breast cancer cells adhesion capacities.
BioMed Research International, 2015
Dengue fever (DF) is the most prevalent arthropod-borne viral disease which affects humans. DF is... more Dengue fever (DF) is the most prevalent arthropod-borne viral disease which affects humans. DF is caused by the four dengue virus (DENV) serotypes, which are transmitted to the host by the mosquito Aedes aegypti that has key roles in DENV infection, replication, and viral transmission (vector competence). Mosquito saliva also plays an important role during DENV transmission. In this study, we detected the presence of sialic acid (Sia) in Aedes aegypti tissues, which may have an important role during DENVvector competence. We also identified genome sequences encoding enzymes involved in Sia pathways. The cDNA for Aedes aegypti CMP-Sia synthase (CSAS) was amplified, cloned, and functionally evaluated via the complementation of LEC29.Lec32 CSASdeficient CHO cells. AedesCSAS-transfected LEC29.Lec32 cells were able to express Sia moieties on the cell surface. Sequences related to-2,6-sialyltransferase were detected in the Aedes aegypti genome. Likewise, we identified Sia-2,6-DENV interactions in different mosquito tissues. In addition, we evaluated the possible role of sialylated molecules in a salivary gland extract during DENV internalization in mammalian cells. The knowledge of early DENV-host interactions could facilitate a better understanding of viral tropism and pathogenesis to allow the development of new strategies for controlling DENV transmission.
International Journal of Oncology, May 13, 2016
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
Glycoconjugate Journal, Sep 19, 2009
Biochemical Journal, Nov 7, 2000
On the basis of the detection of expressed sequence tag (' EST ') similar to the rat N-acetylgala... more On the basis of the detection of expressed sequence tag (' EST ') similar to the rat N-acetylgalactosamine α2,6-sialyltransferase (ST6GalNAc) III cDNA, we have identified a novel member of the human ST6GalNAc family. We have isolated a cDNA clone containing an open reading frame that codes for a type II membrane protein of 302 amino acids with a seven-amino-acid cytoplasmic domain, an 18-amino-acid transmembrane domain and the smallest described catalytic domain of 277 amino acids. This predicted sialyltransferase sequence is similar to the rat ST6GalNAc III (46.6 %), but was found to be even more similar to the recently reported mouse ST6GalNAc IV (88.1 %) on the basis of amino acid sequence identity. Northern-blot analysis showed that the newly identified gene is expressed constitutively in various adult human tissues as a 2.2 kb transcript, but was also found to be expressed at lower levels in brain, heart and skeletal muscle as a 2.5 kb transcript. Expression of the hST6GalNAc IV
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Papers by Philippe Delannoy