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Ganglioside D3

Andreia Hanada Otake, Renata de Freitas Saito, Ana Paula Marques Duarte, Alexandre Ferreira Ramos, Roger Chammas
Melanomas often accumulate gangliosides, sialic acid-containing glycosphingolipids found in the outer leaflet of plasma membranes, as disialoganglioside GD3 and its derivatives. Here, we have transfected the GD3 synthase gene (ST8Sia I) in a normal melanocyte cell line in order to evaluate changes in the biological behavior of non-transformed cells. GD3 -synthase expressing cells converted GM3 into GD3 and accumulated both GD3 and its acetylated form, 9-O-acetyl-GD3 . Melanocytes were rendered more migratory on laminin-1 surfaces...
June 14, 2018: Biochimica et biophysica acta. Molecular and cell biology of lipids
Jonathan M Eby, Levi Barse, Steven W Henning, Martijn J W E Rabelink, Jared Klarquist, Emily R Gilbert, Adam M Hammer, Manuel F Fernandez, Nathan Yung, Safia Khan, Hannah G Miller, Edward R Kessler, Elizabeth Garrett-Mayer, Daniel F Dilling, Rob C Hoeben, I Caroline Le Poole
An immunotherapeutic strategy is discussed supporting anti-tumor activity toward malignancies overexpressing ganglioside D3. GD3 can be targeted by NKT cells when derived moieties are presented in the context of CD1d. NKT cells can support anti-tumor responses by secreting inflammatory cytokines and through cytotoxicity toward CD1d+ GD3+ tumors. To overexpress GD3, we generated expression vector DNA and an adenoviral vector encoding the enzyme responsible for generating GD3 from its ubiquitous precursor GM3...
January 2017: Cancer Immunology, Immunotherapy: CII
Shih-Chi Yeh, Pao-Yuan Wang, Yi-Wei Lou, Kay-Hooi Khoo, Michael Hsiao, Tsui-Ling Hsu, Chi-Huey Wong
The cancer stem cells (CSCs) of glioblastoma multiforme (GBM), a grade IV astrocytoma, have been enriched by the expressed marker CD133. However, recent studies have shown that CD133(-) cells also possess tumor-initiating potential. By analysis of gangliosides on various cells, we show that ganglioside D3 (GD3) is overexpressed on eight neurospheres and tumor cells; in combination with CD133, the sorted cells exhibit a higher expression of stemness genes and self-renewal potential; and as few as six cells will form neurospheres and 20-30 cells will grow tumor in mice...
May 17, 2016: Proceedings of the National Academy of Sciences of the United States of America
Emily R Gilbert, Jonathan M Eby, Adam M Hammer, Jared Klarquist, David G Christensen, Allison J Barfuss, Raymond E Boissy, Maria M Picken, Robert B Love, Daniel F Dilling, I Caroline Le Poole
Tumors that develop in lymphangioleiomyomatosis (LAM) as a consequence of biallelic loss of TSC1 or TSC2 gene function express melanoma differentiation antigens. However, the percentage of LAM cells expressing these melanosomal antigens is limited. Here, we report the overexpression of ganglioside D3 (GD3) in LAM. GD3 is a tumor-associated antigen otherwise found in melanoma and neuroendocrine tumors; normal expression is largely restricted to neuronal cells in the brain. We also observed markedly reduced serum antibody titers to GD3, which may allow for a population of GD3-expressing LAM cells to expand within patients...
July 2013: American Journal of Pathology
Marie Bobowski, Audrey Vincent, Agata Steenackers, Florent Colomb, Isabelle Van Seuningen, Sylvain Julien, Philippe Delannoy
Recent data have underlined a possible role of G(D3) synthase (GD3S) and complex gangliosides in Estrogen Receptor (ER) negative breast cancer progression. Here, we describe the main transcript of the GD3S coding gene ST8SIA1 expressed in breast tumors. We characterized the corresponding core promoter in Hs578T breast cancer cells and showed that estradiol decreases ST8SIA1 mRNA expression in ER-positive MCF-7 cells and ERα-transfected ER-negative Hs578T cells. The activity of the core promoter sequence of ST8SIA1 is also repressed by estradiol...
2013: PloS One
Agata Steenackers, Jorick Vanbeselaere, Aurélie Cazet, Marie Bobowski, Yoann Rombouts, Florent Colomb, Xuefen Le Bourhis, Yann Guérardel, Philippe Delannoy
Glycosphingolipids from the ganglio-series are usually classified in four series according to the presence of 0 to 3 sialic acid residues linked to lactosylceramide. The transfer of sialic acid is catalyzed in the Golgi apparatus by specific sialyltransferases that show high specificity toward glycolipid substrates. ST8Sia I (EC, SAT-II, SIAT 8a) is the key enzyme controlling the biosynthesis of b- and c-series gangliosides. ST8Sia I is expressed at early developmental stages whereas in adult human tissues, ST8Sia I transcripts are essentially detected in brain...
2012: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Aurélie Cazet, Marie Bobowski, Yoann Rombouts, Jonathan Lefebvre, Agata Steenackers, Iuliana Popa, Yann Guérardel, Xuefen Le Bourhis, David Tulasne, Philippe Delannoy
We have recently established and characterized cellular clones deriving from MDA-MB-231 breast cancer cells that express the human G(D3) synthase (GD3S), the enzyme that controls the biosynthesis of b- and c-series gangliosides. The GD3S positive clones show a proliferative phenotype in the absence of serum or growth factors and an increased tumor growth in severe immunodeficient mice. This phenotype results from the constitutive activation of the receptor tyrosine kinase c-Met in spite of the absence of ligand and subsequent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase and phosphoinositide 3-kinase/Akt pathways...
June 2012: Glycobiology
O S Jørgensen, D G Stein
Transplants of fetal brain tissue or injections of ganglioside GM1, given to rats with unilateral, left medial frontal cortex lesions, altered the concentrations of neuronal and glial marker proteins in cortex both adjacent and contralateral to the lesion. The markers were: the neural cell adhesion molecule (NCAM) and D3-protein, both present in neuronal and synaptic membranes; synaptophysin, present in synaptic vesicles; glial fibrillary acidic protein (GFAP) enriched in reactive astrocytes, and the astrocytic glutamine synthetase...
January 1, 1992: Restorative Neurology and Neuroscience
Sanhong Yu, Margherita T Cantorna
Vitamin D status changes with season, but the effect of these changes on immune function is not clear. In this study, we show that in utero vitamin D deficiency in mice results in a significant reduction in invariant NKT (iNKT) cell numbers that could not be corrected by later intervention with vitamin D or 1,25-dihydroxy vitamin D(3) (active form of the vitamin). Furthermore, this was intrinsic to hematopoietic cells, as vitamin D-deficient bone marrow is specifically defective in generating iNKT cells in wild-type recipients...
February 1, 2011: Journal of Immunology: Official Journal of the American Association of Immunologists
Aurélie Cazet, Jonathan Lefebvre, Eric Adriaenssens, Sylvain Julien, Marie Bobowski, Anita Grigoriadis, Andrew Tutt, David Tulasne, Xuefen Le Bourhis, Philippe Delannoy
The disialoganglioside G(D3) is overexpressed in ∼50% of invasive ductal breast carcinoma, and the G(D3) synthase gene (ST8SIA1) displays higher expression among estrogen receptor-negative breast cancer tumors, associated with a decreased overall survival of breast cancer patients. However, no relationship between ganglioside expression and breast cancer development and aggressiveness has been reported. We have previously shown that overexpression of G(D3) synthase induces the accumulation of b- and c-series gangliosides (G(D3), G(D2), and G(T3)) at the cell surface of MDA-MB-231 breast cancer cells together with the acquisition of a proliferative phenotype in the absence of serum...
November 2010: Molecular Cancer Research: MCR
Enrico Scala, Damiano Abeni, Debora Pomponi, Maria Grazia Narducci, Giuseppe Alfonso Lombardo, Adriano Mari, Marina Frontani, Maria Cristina Picchio, Maria Antonietta Pilla, Elisabetta Caprini, Giandomenico Russo
BACKGROUND: Sézary syndrome is a rare and very aggressive leukemic variant of cutaneous T-cell lymphoma characterized by extensive skin involvement and a malignant circulating CD4(+) T-cell clone which homes to the skin, over-expresses CD60, and lacks CD7, CD26 and CD49d. So far prognostic markers in this disease are limited to treatment with systemic steroids, age, serum lactate dehydrogenase, and a white blood cell count of 20×10(9)/L or higher: no other biological marker with prognostic value, especially related to malignant cells, has been described...
November 2010: Haematologica
Lionel Batista, Florence Miller, Céline Clave, Audrey Arfi, Gaëlle Douillard-Guilloux, Pierre-Olivier Couraud, Catherine Caillaud
Sandhoff disease is an autosomal recessive lysosomal disorder due to mutations in the beta-hexosaminidase beta-chain gene, resulting in beta-hexosaminidases A (alphabeta) and B (betabeta) deficiency and GM2 ganglioside accumulation in the brain. In this study, our aim was to demonstrate that transduction of cerebral endothelial cells cultured in two-chamber culture inserts with a lentiviral vector encoding the hexosaminidases alpha and beta chains could induce a vectorial secretion of hexosaminidases. Therefore, the human cerebral endothelial cell line hCMEC/D3 was infected with the bicistronic vector from the apical compartment, and beta-hexosaminidase activity was measured in transduced cells and in deficient fibroblasts co-cultured in the basal (i...
March 2010: Neurobiology of Disease
Aurélie Cazet, Sophie Groux-Degroote, Béatrice Teylaert, Kyung-Min Kwon, Sylvain Lehoux, Christian Slomianny, Cheorl-Ho Kim, Xuefen Le Bourhis, Philippe Delannoy
The disialoganglioside G(D3) is an oncofetal marker of a variety of human tumors including melanoma and neuroblastoma, playing a key role in tumor progression. G(D3) and 9-O-acetyl-G(D3) are overexpressed in approximately 50% of invasive ductal breast carcinoma, but no relationship has been established between disialoganglioside expression and breast cancer progression. In order to determine the effect of G(D3) expression on breast cancer development, we analyzed the biosynthesis of gangliosides in several breast epithelial cell lines including MDA-MB-231, MCF-7, BT-20, T47-D, and MCF10A, by immunocytochemistry, flow cytometry, and real-time PCR...
July 2009: Biological Chemistry
Beatrix Kotlan, Peter Simsa, Jean-Luc Teillaud, Wolf Herman Fridman, Jozsef Toth, Michael McKnight, Mark C Glassy
The potential tumor-recognizing capacity of B cells infiltrating human breast carcinoma is an important aspect of breast cancer biology. As an experimental system, we used human medullary breast carcinoma because of its heavy B lymphocytic infiltration paralleled to a relatively better prognosis. Ig-rearranged V region V(H)-J(H), Vkappa-Jkappa, and Vlambda-Jlambda genes, amplified by RT-PCR of the infiltrating B cells, were cloned, sequenced, and subjected to a comparative DNA analysis. A combinatorial single-chain variable fragment Ab minilibrary was constructed out of randomly selected V(H) and Vkappa clones and tested for binding activity...
August 15, 2005: Journal of Immunology: Official Journal of the American Association of Immunologists
Kazunori Yamaguchi, Keiko Hata, Koichi Koseki, Kazuhiro Shiozaki, Hirotoshi Akita, Tadashi Wada, Setsuko Moriya, Taeko Miyagi
Based on the human cDNA sequence predicted to represent the NEU4 sialidase gene in public databases, a cDNA covering the entire coding sequence was isolated from human brain and expressed in mammalian cells. The cDNA encodes two isoforms: one possessing an N-terminal 12-amino-acid sequence that is predicted to be a mitochondrial targeting sequence, and the other lacking these amino acids. Expression of the isoforms is tissue specific, as assessed by reverse transcription-PCR. Brain, muscle and kidney contained both isoforms; liver showed the highest expression, and the short form was predominant in this organ...
August 15, 2005: Biochemical Journal
I C Le Poole, L S Stennett, B K Bonish, L Dee, J K Robinson, C Hernandez, S K Hann, B J Nickoloff
BACKGROUND: Detection of CDw60 in skin is representative of ganglioside D3 expression. This ganglioside is expressed primarily by melanocytes, and is of interest as a membrane antigen targeted by immunotherapy for melanoma patients. Expression of CDw60 by keratinocytes is defined by the presence of T-helper cell (Th)1 vs. Th2 cytokines, and can serve as a sentinel molecule to characterize an ongoing skin immune response. OBJECTIVES: These immunobiological characteristics have provided the incentive to study the expression of CDw60 in the context of progressive vitiligo...
October 2003: British Journal of Dermatology
Pilar M Crespo, Adolfo R Zurita, Claudio G Giraudo, Hugo J F Maccioni, Jose L Daniotti
GEM (glycosphingolipid-enriched microdomains) are specialized detergent-resistant domains of the plasma membrane in which some gangliosides concentrate. Although genesis of GEM is considered to occur in the Golgi complex, where the synthesis of gangliosides also occurs, the issue concerning the incorporation of ganglioside species into GEM is still poorly understood. In this work, using Chinese hamster ovary K1 cell clones with different glycolipid compositions, we compared the behaviour with cold Triton X-100 solubilization of plasma membrane ganglioside species with the same species newly synthesized in Golgi membranes...
February 1, 2004: Biochemical Journal
Dominique Ardail, Iuliana Popa, Jacques Bodennec, Pierre Louisot, Daniel Schmitt, Jacques Portoukalian
Although most glycosphingolipids (GSLs) are thought to be located in the outer leaflet of the plasma membrane, recent evidence indicates that GSLs and their precursor, ceramide, are also associated with intracellular organelles and, particularly, mitochondria. GSL biosynthesis starts with the formation of ceramide in the endoplasmic reticulum (ER), which is transported by controversial mechanisms to the Golgi apparatus, where stepwise addition of monosaccharides on to ceramides takes place. We now report the presence of GSL-biosynthetic enzymes in a subcompartment of the ER previously characterized and termed 'mitochondria-associated membrane' (MAM)...
May 1, 2003: Biochemical Journal
F Martini, S Riondino, P Pignatelli, P P Gazzaniga, P Ferroni, L Lenti
Gangliosides are sialic acid-containing glycosphingolipids present in the outer leaflet of the plasma membrane of many cell types where they modulate adhesive processes. The main population of glycolipids in resting platelets is represented by ganglioside M3 (GM3). It has been demonstrated that following platelet activation ganglioside D3 (GD3) is rapidly formed from the GM3 pool. The present study was designed to evaluate the link between platelet activation and GD3 expression and to verify whether this ganglioside might play a role in modulating signal transduction events...
August 8, 2002: Biochimica et Biophysica Acta
A G Buggins, D Milojkovic, M J Arno, N C Lea, G J Mufti, N S Thomas, W J Hirst
Tumors produce a variety of immunosuppressive factors which can prevent the proliferation and maturation of a number of normal hemopoietic cell types. We have investigated whether primary acute myeloid leukemia (AML) cells have an effect on normal T cell function and signaling. Tumor cell supernatant (TSN) from AML cells inhibited T cell activation and Th1 cytokine production and also prevented activated T cells from entering the cell cycle. These effects occurred in the absence of AML cell-T cell contact. We have demonstrated that AML TSN contained none of the immunosuppressors described to date, namely gangliosides, nitric oxide, TGF-beta, IL-10, vascular endothelial growth factor, or PGs...
November 15, 2001: Journal of Immunology: Official Journal of the American Association of Immunologists
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