Abstract:
:Proteoglycans and glycosaminoglycans modulate numerous cellular processes relevant to tumour progression, including cell proliferation, cell-matrix interactions, cell motility and invasive growth. Among the glycosaminoglycans with a well-documented role in tumour progression are heparan sulphate, chondroitin/dermatan sulphate and hyaluronic acid/hyaluronan. While the mode of biosynthesis differs for sulphated glycosaminoglycans, which are synthesised in the ER and Golgi compartments, and hyaluronan, which is synthesized at the plasma membrane, these polysaccharides partially compete for common substrates. In this study, we employed a siRNA knockdown approach for heparan sulphate (EXT1) and heparan/chondroitin/dermatan sulphate-biosynthetic enzymes (β4GalT7) in the aggressive human breast cancer cell line MDA-MB-231 to study the impact on cell behaviour and hyaluronan biosynthesis. Knockdown of β4GalT7 expression resulted in a decrease in cell viability, motility and adhesion to fibronectin, while these parameters were unchanged in EXT1-silenced cells. Importantly, these changes were associated with a decreased expression of syndecan-1, decreased signalling response to HGF and an increase in the synthesis of hyaluronan, due to an upregulation of the hyaluronan synthases HAS2 and HAS3. Interestingly, EXT1-depleted cells showed a downregulation of the UDP-sugar transporter SLC35D1, whereas SLC35D2 was downregulated in β4GalT7-depleted cells, indicating an intricate regulatory network that connects all glycosaminoglycans synthesis. The results of our in vitro study suggest that a modulation of breast cancer cell behaviour via interference with heparan sulphate biosynthesis may result in a compensatory upregulation of hyaluronan biosynthesis. These findings have important implications for the development of glycosaminoglycan-targeted therapeutic approaches for malignant diseases.
journal_name
Glycoconj Jjournal_title
Glycoconjugate journalauthors
Viola M,Brüggemann K,Karousou E,Caon I,Caravà E,Vigetti D,Greve B,Stock C,De Luca G,Passi A,Götte Mdoi
10.1007/s10719-016-9735-6subject
Has Abstractpub_date
2017-06-01 00:00:00pages
411-420issue
3eissn
0282-0080issn
1573-4986pii
10.1007/s10719-016-9735-6journal_volume
34pub_type
杂志文章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::Serum GP73 is a functional resident Golgi type II membrane protein with three potential N-glycosylation sites. In this study, we used multiple lectin assays to analyze glycan patterns of serum GP73 and evaluated its diagnostic value for distinguishing hepatocellular carcinoma (HCC) from liver cirrhosis (LC). Firstly, ...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-015-9614-6
更新日期:2015-12-01 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::The complex microenvironment that surrounds hematopoietic stem cells (HSCs) in the bone marrow niche involves different coordinated signaling pathways. The stem cells establish permanent interactions with distinct cell types such as mesenchymal stromal cells, osteoblasts, osteoclasts or endothelial cells and with secr...
journal_title:Glycoconjugate journal
pub_type: 杂志文章,评审
doi:10.1007/s10719-017-9773-8
更新日期:2017-06-01 00:00:00
abstract::Galectins are animal lectins that can specifically bind beta-galactosides. Thirteen galectins have already been described. This review focuses on a specific member of this family: galectin-8. This galectin was discovered in prostate cancer cells eight years ago and has been studied extensively in the last few years. T...
journal_title:Glycoconjugate journal
pub_type: 杂志文章,评审
doi:10.1023/B:GLYC.0000014086.38343.98
更新日期:2002-01-01 00:00:00
abstract::Heterologous complementation in yeast has been a successful tool for cloning and characterisation of genes from various organisms. Therefore we constructed conditionally lethal Saccharomyces cerevisiae strains by replacing the endogenous promoter from the genes of interest (glycosyltransferases) by the stringently reg...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1007132907235
更新日期:1999-11-01 00:00:00
abstract::Strongly reacting antibodies specific for defined mucin gene products are often directed against the mucin protein backbone of the heavily glycosylated serine/threonine rich regions. A prerequisite for the use of such antibodies is often the complete removal of the oligosaccharides from the protein. This paper describ...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1006935227730
更新日期:1998-08-01 00:00:00
abstract::Exposure of neuronal cells to nanomolar concentrations of oligosaccharide portions of ganglioside GM2 and GT1b stimulates cAMP-dependent protein kinase (PKA) Ca2+/calmodulin-dependent protein kinase II (CaMKII), respectively, in a few seconds suggesting the presence of glyco-receptor-like molecules on the surface of t...
journal_title:Glycoconjugate journal
pub_type: 杂志文章,评审
doi:10.1023/B:GLYC.0000016742.88750.1a
更新日期:2004-01-01 00:00:00
abstract::C-Mannosylation, a protein-modification found in various eukaryotes, involves the attachment of a single mannose molecule to selected tryptophan residues of proteins. Since C-mannosyl tryptophan (CMW) was detected in human urine, it is generally thought that CMW is not catabolized inside our body and instead is excret...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-017-9807-2
更新日期:2018-04-01 00:00:00
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journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1006901803636
更新日期:1999-01-01 00:00:00
abstract::The human glioma D-54MG cell line grown in vitro primarily expresses ganglio series gangliosides, particularly GM2. Subcutaneous injection of these cells into nude mice produced xenografts with an increased content of the human glioma-associated lacto series gangliosides, primarily 3'-isoLM1, an alteration that was do...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/BF00731472
更新日期:1996-06-01 00:00:00
abstract::Sulfated galactans (SGs) are highly anionic marine galactose-composed homopolysaccharides. Although their structures vary among species, their main features are conserved among phyla. Green algal SGs are quite heterogeneous, although preponderantly composed of 3-beta-D-Galp units. The red algal SGs (like agar and carr...
journal_title:Glycoconjugate journal
pub_type: 杂志文章,评审
doi:10.1007/s10719-009-9251-z
更新日期:2010-01-01 00:00:00
abstract::A monoclonal antibody (mAb 8281) specific for the terminal beta-galactose (beta Gal) of glycosphingolipids (GSL) and glycoproteins was produced from mice immunized with lipid extract from fresh acute lymphocytic leukemia (ALL) cells. Immuno-thin layer chromatography (ITLC) and competition assays with purified neutral ...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/BF00731643
更新日期:1991-02-01 00:00:00
abstract::Duffy antigen/receptor for chemokines (DARC) is a glycosylated seven-transmembrane protein acting as a blood group antigen, a chemokine binding protein and a receptor for Plasmodium vivax malaria parasite. It is present on erythrocytes and endothelial cells of postcapillary venules. The N-terminal extracellular domain...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-011-9367-9
更新日期:2012-04-01 00:00:00
abstract::In this study, the antibody 3G9-A was assayed for activity against human erythrocyte glycosphingolipids. The antibody was found to recognize glycosphingolipid components from blood group A erythrocytes but not glycosphingolipids from blood group B or O erythrocytes. Subsequent investigation revealed that the glycosphi...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/BF00731482
更新日期:1996-06-01 00:00:00
abstract::The IgG Fc glycans strongly influence the Fcγ receptor interactions and Fc-mediated effector mechanisms. Changes in the structure of IgG glycans are associated with various diseases, such as infections and autoimmunity. However, the possible role of Fc glycans in tumor immunity is not yet fully understood. The aim of ...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-011-9364-z
更新日期:2012-01-01 00:00:00
abstract::Rotaviruses are the leading cause of childhood diarrhea. The entry of rotaviruses into the host cell is a complex process that includes several interactions of the outer layer proteins of the virus with different cell surface molecules. The fact that neuraminidase treatment of the cells, or preincubation of the virus ...
journal_title:Glycoconjugate journal
pub_type: 杂志文章,评审
doi:10.1007/s10719-006-5435-y
更新日期:2006-02-01 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::Studying polysaccharide-protein interactions under physiological conditions by conventional techniques is challenging. Ideally, macromolecules could be followed by both in vitro spectroscopy experiments as well as in tissues using microscopy, to enable a proper comparison of results over these different scales but, of...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-016-9723-x
更新日期:2017-06-01 00:00:00
abstract::Diabetic mellitus is attended by the development of endothelial dysfunction which is suggested to be accompanied with a chronic low-degree of inflammation. During a chronic hepatic inflammatory response, specific changes in glycosylation of the acute phase protein alpha1-acid glycoprotein (AGP) can be detected. In thi...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1012412908983
更新日期:2001-03-01 00:00:00
abstract::A group of fluorescent statistical glycopolymers, prepared via reversible addition-fragmentation chain-transfer (RAFT)-based polymerizations, were successfully employed in lectin-mediated bacterial binding studies. The resultant glycopolymers contained three different monomers: N-(2-hydroxyethyl) acrylamide (HEAA), N-...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-013-9508-4
更新日期:2014-02-01 00:00:00
abstract::Macrophages from various origins are known to express membrane lectins that mediate the endocytosis of mannose-bearing glycoconjugates. Most macrophage tumor cell-lines lack such receptors. In this paper we show by flow cytometry analysis that a newly generated macrophage hybridoma (2C11-12), which displays several ma...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/BF01053778
更新日期:1989-01-01 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::Heteropolysaccarides were isolated from the Korean medicinal plant, Phellodendri cortex (Hwangbek), by hot water and alkali extractions. The extracted polysaccharides were fractionated into eight fractions and they are mainly composed of D-N-acetylglucosamine, D-galactose, D-mannose, and D-glucose. Among the polysacch...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1023/a:1007084506071
更新日期:1999-03-01 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::Recently, we demonstrated that the human xylosyltransferase II (XT-II) has enzymatic activity and is able to catalyze the initial and rate-limiting step in the biosynthesis of glycosaminoglycans (GAGs) like chondroitin and dermatan sulfate, as well as heparan sulfate and heparin. Therefore, this enzyme also very likel...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-012-9439-5
更新日期:2013-04-01 00:00:00
abstract::UDP-2-(2-ketopropyl)galactose (1) has been utilized as a valuable probe for profiling proteins modified by O-GlcNAc. In this work, we developed a protocol for efficient synthesis of 1. Thus, 2-methallylgalactose derivative 11, a synthetic intermediate for the compound 1, was prepared by stereoselective iodination and ...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-015-9581-y
更新日期:2015-10-01 00:00:00
abstract::Multidisciplinary approaches by a number of investigators have established that cell-surface carbohydrates are integral components of recognition systems regulating survival, migration, adhesion, growth and differentiation of various cells. Our own experience and contributions to this exciting field are described. We ...
journal_title:Glycoconjugate journal
pub_type: 传,历史文章,杂志文章
doi:10.1023/a:1011078627247
更新日期:2000-07-01 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::Proteoglycans contain a unique carbohydrate component, glycosaminoglycan, which consists of repeating, typically sulfated disaccharides, and is capable of interacting with diverse molecules. Specific, clustered arrangements of sulfate on the glycosaminoglycan backbone form binding sites for many biologically important...
journal_title:Glycoconjugate journal
pub_type: 杂志文章
doi:10.1007/s10719-008-9138-4
更新日期:2009-11-01 00:00:00