Abstract:
:Humans, in contrast to other mammals, do not synthesize N-glycolyl-neuraminic acid (Neu5Gc) due to a deletion in the gene (cmah) encoding the enzyme responsible for this conversion, the cytidine monophospho-N-acetyl-neuraminic acid hydroxylase (CMP-Neu5Ac hydroxylase). The detection of considerable amounts of Neu5Gc-sialoconjugates, in particular gangliosides, in human malignancies makes these antigens attractive targets for immunotherapy, in particular with monoclonal antibodies (mAbs). We have previously described a GM3(Neu5Gc) ganglioside-specific mAb, named 14F7, with the ability to kill tumor cells in a complement-independent manner. Silencing the cmah gene in GM3(Neu5Gc)-expressing L1210 mouse lymphocytic leukemia B cells caused the abrogation of this cytotoxic effect. We now show that cmah-silenced L1210 cells (cmah-kd) express a high level of GM3(Neu5Ac) and have an impaired ability for anchorage-independent cell growth and tumor development in vivo. No evidences of increased immunogenicity of the cmah-kd cell line were found. These results provide new evidences on the role of GM3(Neu5Gc), or Neu5Gc-sialoconjugates in general, in tumor biology. As an important tool in this study, we used the humanized version (here referred to as 7C1 mAb) of a recently described, rationally-designed mutant of 14F7 mAb that is able to bind to both GM3(Neu5Gc) and GM3(Neu5Ac). In contrast to its parental antibody, the humanized 14F7 (14F7hT) mAb, 7C1 mAb was able to kill not only GM3(Neu5Gc)-expressing L1210 wild type cells, but also GM3(Neu5Ac)-expressing cmah-kd cells, which endorses this antibody as a potential agent for cancer immunotherapy.
journal_name
Glycoconj Jjournal_title
Glycoconjugate journalauthors
Casadesús AV,Fernández-Marrero Y,Clavell M,Gómez JA,Hernández T,Moreno E,López-Requena Adoi
10.1007/s10719-013-9473-ysubject
Has Abstractpub_date
2013-10-01 00:00:00pages
687-99issue
7eissn
0282-0080issn
1573-4986journal_volume
30pub_type
杂志文章abstract::Full proton NMR assignments have been achieved for the alpha(1-3)-linked fucose residues contained in alkaline borohydride reduced keratan sulphate chains derived from bovine articular cartilage. This involved 500 MHz spectroscopy at 60 degrees C and included COSY and RELAYED-COSY determinations. ...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/BF00731641
更新日期:1991-02-01 00:00:00
abstract::In aging and diabetes, glycation of collagen molecules leads to the formation of cross-links that could alter the surface charge on collagen fibrils, and hence affect the properties and correct functioning of a number of tissues. The electron-optical stain phosphotungstic acid (PTA) binds to positively charged amino a...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1006928403140
更新日期:1998-08-01 00:00:00
abstract::The metabolism of glycosphingolipids is strictly regulated during the mitotic cell cycle. Before the G1-to-S transition, the ceramide and glucosylceramide concentration is elevated. Ceramide induces apoptosis synergistically with the pro-apoptotic protein prostate apoptosis response 4 (PAR-4) that may be asymmetricall...
journal_title:Glycoconjugate journal
pub_type: 杂志文章,评审
doi:10.1023/B:GLYC.0000046274.35732.47
更新日期:2004-01-01 00:00:00
abstract::Glycation (nonenzymatic glycosylation) in the human lens (cortex and nucleus) in senile (nondiabetic) and diabetic cataracts was studied by measuring the extent of early and late glycation products, the content of free epsilon-amino groups and the formation of disulfide bonds in the soluble lens proteins. There was a ...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/BF00731255
更新日期:1995-10-01 00:00:00
abstract::Syndecan-4 is a transmembrane heparan sulfate proteoglycan belonging to the syndecan family. Syndecan-4-deficient [(Synd4(-/-)] mice were produced to clarify the in vivo role of syndecan-4. Synd4(-/-) mice were more susceptible to kappa-carrageenan-induced nephropathy, and the placental labyrinth from the deficient em...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/A:1025308702966
更新日期:2002-05-01 00:00:00
abstract::By employing a bovine UDP-N-acetylgalactosamine: polypeptide N-acetylgalactosaminyl transferase (O-GalNAc transferase) cDNA as a probe, we isolated four overlapping cDNAs from a porcine lung cDNA library. Both the nucleotide sequence of the porcine cDNA and the predicted primary structure of the protein (559 amino aci...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/BF00731244
更新日期:1995-12-01 00:00:00
abstract::We analyzed surface glycoproteins of human natural killer (NK) cells by utilizing lectins. Among the lectins tested, wheat germ agglutinin (WGA) was found to bind preferentially to CD16(Leu11)-positive lymphocytes as determined by two-colour flow cytometry. Analysis of glycoproteins in the lysate prepared from NK cell...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/BF00731165
更新日期:1992-08-01 00:00:00
abstract::Oral exposure to lectins or the presence or absence of bacteria in the rat small intestine were shown by histological methods using anti-lectin antibodies or digoxigenin-labelled lectins to have major effects on the state of glycosylation of lumenal membranes and cytoplasmic glycoconjugates of epithelial cells. Taken ...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/BF00731865
更新日期:1995-02-01 00:00:00
abstract::A straight forward synthesis of a heptasaccharide part of the cell-wall lipopolysaccharide of Mycobacterium gordonae strain 990, known to have antigenicity, has been achieved in excellent yield. Judicious choice of protecting groups in the intermediates played a significant role throughout the synthesis. Most of the i...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-008-9142-8
更新日期:2008-12-01 00:00:00
abstract::The N-glycan moiety of ascorbic acid oxidase from zucchini (Cucurbita pepo) has been described to be a core-pentasaccharide with a xylose [D'Andrea et al. (1988) Glycoconjugate J 5:151-7]. Ascorbic acid oxidase is sometimes used to characterize antibodies directed against carbohydrate determinants on plant glycoprotei...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1006947701714
更新日期:1998-01-01 00:00:00
abstract::The small keratan sulphate proteoglycan, fibromodulin, has been isolated from pooled human articular cartilage. The main chain repeat region and the chain caps from the attached N-linked keratan sulphate chains have been fragmented by keratanase II digestion, and the oligosaccharides generated have been reduced and is...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1018552913584
更新日期:1997-08-01 00:00:00
abstract::Comparing the properties of 'young' and senescent ('aged') O+ erythrocytes isolated by applying ultracentrifugation in a self-forming Percoll gradient, we demonstrate that the sialic acids of membrane glycoconjugates control the life span of erythrocytes and that the desialylation of glycans is responsible for the cle...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/BF00731328
更新日期:1995-06-01 00:00:00
abstract::Transmembrane signaling requires modular interactions between signaling proteins, phosphorylation or dephosphorylation of the interacting protein partners and temporary elaboration of supramolecular structures, to convey the molecular information from the cell surface to the nucleus. Such signaling complexes at the pl...
journal_title:Glycoconjugate journal
pub_type: 杂志文章,评审
doi:10.1023/a:1026585006064
更新日期:2000-03-01 00:00:00
abstract::The main component of the ganglioside(1) mixture from the brain of the adult amphibian Xenopus laevis accounts for 35% of the total, as lipid bound sialic acid. This ganglioside has been purified and characterized by thin layer chromatography, partial and exhaustive enzymatic hydrolysis with sialidase, TLC-overlay pro...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1022584914778
更新日期:2002-01-01 00:00:00
abstract::Stage-specific embryonic antigen-4 (SSEA-4), a specific marker for pluripotent stem cells, plays an important role in the malignant behavior of several cancers. Here, SSEA-4 expression was evaluated by immunohistochemistry using monoclonal antibody RM1 specific to SSEA-4 in 181 and 117 prostate cancer (PC) specimens o...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-019-09882-2
更新日期:2019-10-01 00:00:00
abstract::UDP-GlcNAc:alpha6-D-mannoside beta1,2-N-acetylglucosaminyltransferase II (GnT II; EC 2.4.1.143) is a medial-Golgi resident enzyme that catalyses an essential step in the biosynthetic pathway leading from high mannose to complex N-linked oligosaccharides. Screening a cDNA library from Xenopus laevis ovary with a human ...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/A:1024201824354
更新日期:2002-03-01 00:00:00
abstract::Lubrication of mammalian joints is mediated by lubricin, a product of megakaryocyte stimulating factor gene (MSF; GenBank accession #U70136) expression. Lubricin (M(r) approximately 240 kDa) is a mucinous glycoprotein which is 50% (w/w) post-translationally modified with beta(1-3)Gal-GalNAc incompletely capped with Ne...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1021159619373
更新日期:2001-10-01 00:00:00
abstract::Glycans serve as important regulators of antibody activities and half-lives. IgE is the most heavily glycosylated antibody, but in comparison to other antibodies little is known about its glycan structure function relationships. We therefore describe the site specific IgE glycosylation from a patient with a novel hype...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-015-9638-y
更新日期:2016-06-01 00:00:00
abstract::Mammalian sulfoglycolipids are comprised of two major members, sulfatide (SO(3)-3Gal-ceramide) and seminolipid (SO(3)-3Gal-alkylacylglycerol). Sulfatide is abundant in the myelin sheath and seminolipid is expressed on the spermatogenic cells. Cerebroside sulfotransferase (CST)-deficient mice generated by gene targetin...
journal_title:Glycoconjugate journal
pub_type: 杂志文章,评审
doi:10.1023/B:GLYC.0000043749.06556.3d
更新日期:2004-01-01 00:00:00
abstract::Previous studies had established an over-expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac(2)-GPs) on lymphoblasts of childhood acute lymphoblastic leukaemia (ALL). Here, we report the discovery and characterization of sialate-O-acetyltransferase enzyme in ALL-cell lines and lymphoblasts from bone marrow of ch...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-008-9163-3
更新日期:2009-01-01 00:00:00
abstract::Human β-1,4-galactosyltransferase (β-1,4-GalT) V was shown to be involved in the biosynthesis of N-glycans, O-glycans and lactosylceramide (Lac-Cer) by in vitro studies. To determine its substrate specificity, enzymatic activity and its products were analyzed using mouse embryonic fibroblast (MEF) cells from β-1,4-Gal...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-010-9313-2
更新日期:2010-10-01 00:00:00
abstract::Carbohydrate-carbohydrate interaction is a reliable and versatile mechanism for cell adhesion and recognition. Glycosphingolipid (GSL) clusters at the cell membrane are mainly involved in this interaction. To investigate carbohydrate-carbohydrate interaction an integrated strategy (Glyconanotechnology) was developed. ...
journal_title:Glycoconjugate journal
pub_type: 杂志文章,评审
doi:10.1023/B:GLYC.0000044846.80014.cb
更新日期:2004-01-01 00:00:00
abstract::Cell surface lipopolysaccharide (LPS) is a well characterized virulence determinant for the human pathogen Haemophilus influenzae, so an investigation of LPS in the less pathogenic Haemophilus parainfluenzae could yield important insights. Using a panel of 18 commensal H. parainfluenzae isolates we demonstrate that th...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-012-9455-5
更新日期:2013-08-01 00:00:00
abstract::The partial oligosaccharide sequences of glycoconjugates and the nature of their glycosidic linkages were investigated in normal human prostate, benign prostatic hyperplasia (BPH) and prostatic carcinoma by means of lectin histochemistry, using light microscopy and Western blot analysis. The labeling pattern of BPH di...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1007012514118
更新日期:1999-07-01 00:00:00
abstract::Twenty different human and animal tissues were investigated for the presence of polyglycosylceramides. The glycolipids were isolated by peracetylation of dry tissue residues left after conventional lipid extraction, followed by extraction with chloroform and subsequent Sephadex LH-20, Sephadex LH-60 and silica gel chr...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1018545922728
更新日期:1997-02-01 00:00:00
abstract::Archaea are ubiquitous single-cell microorganisms that have often adapted to harsh conditions and play important roles in biogeochemical cycles with potential applications in biotechnology. Methanococcus maripaludis, a methane-producing archaeon, is motile through multiple archaella on its cell surface. The major stru...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-018-9845-4
更新日期:2018-12-01 00:00:00
abstract::Our recent studies have revealed the existence of two distinct Gal: 3-O-sulfotransferases capable of acting on the C-3 position of galactose in a Core 2 branched structure, e.g., Galbeta1-->4GlcNAcbeta1-->6(Galbeta1-->3)GalNacalph a1-->OBenzyl as acceptor to give 3-O-sulfoGalbeta1-->4GlcNAcbeta1-->3(Galbeta1-->3)G alN...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1006977607394
更新日期:1998-10-01 00:00:00
abstract::Disialosyl globopentaosylceramide (DSGb5) is a ganglioside originally isolated from tissue extracts of renal cell carcinoma (RCC) with metastasis. Previous in vitro experiments have suggested that DSGb5 promotes metastasis by enhancing the migration of RCC cells and downregulating NK cell cytotoxicity against RCC cell...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-017-9763-x
更新日期:2017-04-01 00:00:00
abstract::Matrix proteoglycans (PGs) have shown promise as biomarker in malignancies. We employed agarose gel eletrophoresis, quantitative real- time reverse transcription-polymerase chain reaction and immunohistochemistry to evaluate the content of sulfated glicosaminoglycans (chondroitin sulfate and heparan sulfate) and expre...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-018-9815-x
更新日期:2018-04-01 00:00:00
abstract::In this report we present the enzymatic characterization of CMP-NeuAc:Gal beta 1-4GlcNAc-R alpha(2-3)-sialyltransferase from human placenta using placenta membranes as an enzyme preparation. This sialyltransferase is highly sensitive to detergents and prefers type 2 chain (Gal beta 1-4GlcNAc) over type 1 chain (Gal be...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/BF00731193
更新日期:1993-02-01 00:00:00