Keratan sulfate levels in sera of patients bearing cartilage tumors

Kliner, Dale J.; Gorski, Jeffrey P.; Thonar, Eugene J.‐M.A.

doi:10.1002/1097-0142(19870601)59:11<1931::aid-cncr2820591116>3.0.co;2-7

Cited by 11 publications

(5 citation statements)

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“…In particular, chondroitin sulfate proteoglycans have been shown to accumulate in cancer cells and promote tumorigenesis by interacting with surface receptors [ 68 ]. Furthermore, keratan sulfate has been shown to accumulate in the serum of patients with cartilage tumors, and serum levels were shown to decrease upon tumor removal [ 69 ]. Our results suggest that this accumulation is coupled with a down-regulation of glycosaminoglycans degradation.…”

Section: Discussionmentioning

confidence: 99%

Reconstruction of Tissue-Specific Metabolic Networks Using CORDA

2016

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Human metabolism involves thousands of reactions and metabolites. To interpret this complexity, computational modeling becomes an essential experimental tool. One of the most popular techniques to study human metabolism as a whole is genome scale modeling. A key challenge to applying genome scale modeling is identifying critical metabolic reactions across diverse human tissues. Here we introduce a novel algorithm called Cost Optimization Reaction Dependency Assessment (CORDA) to build genome scale models in a tissue-specific manner. CORDA performs more efficiently computationally, shows better agreement to experimental data, and displays better model functionality and capacity when compared to previous algorithms. CORDA also returns reaction associations that can greatly assist in any manual curation to be performed following the automated reconstruction process. Using CORDA, we developed a library of 76 healthy and 20 cancer tissue-specific reconstructions. These reconstructions identified which metabolic pathways are shared across diverse human tissues. Moreover, we identified changes in reactions and pathways that are differentially included and present different capacity profiles in cancer compared to healthy tissues, including up-regulation of folate metabolism, the down-regulation of thiamine metabolism, and tight regulation of oxidative phosphorylation.

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Section: Discussionmentioning

confidence: 99%

Reconstruction of Tissue-Specific Metabolic Networks Using CORDA

2016

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“…KS is mainly found in cartilage-type proteoglycan aggregates (aggrecans; approximately 99%) and to a lesser degree in the cornea and other tissues [2]. Therefore KS concentration, as a metabolite of cartilage, is measured in the synovial fluid and blood to estimate the damage of cartilage in patients with osteoarthritis and rheumatoid arthritis [3,12,26,30,31].…”

Section: Methodsmentioning

confidence: 99%

Consideration of the Role of Antigenic Keratan Sulphate Reacting to a 1/14/16H9 Antibody as a Molecular Marker to Monitor Cartilage Metabolism in Horses

Okumura

Tagami²,

Fujinaga

2000

The Journal of Veterinary Medical Science

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ABSTRACT. The role of keratan sulphate (KS) as a marker of cartilage metabolism was evaluated by using an in vitro model of equine articular cartilage. Articular cartilage was harvested from clinically healthy 6-month-old foals (n=3). Chondrocytes were centrifuged and cultured as pellets. Chondrocyte pellets were stimulated by insulin-like growth factor (IGF)-Iα or interleukin (IL)-1α for 2 weeks. The sulfated glycosaminoglycans (GAG) and antigenic KS concentrations in the culture media were measured by a 1,9-dimethyl-methylene blue (DMMB) colorimetric assay and an inhibition ELISA using a 1/14/16H9 antibody, respectively. Concentration of GAG was significantly increased in the media of pellets stimulated by both IGF-Iα and IL-1α. Antigenic KS concentration was significantly increased in those stimulated by IL-1α, while no significant change was found in those stimulated by IGF-Iα. A high correlation between GAG and antigenic KS concentrations was found in the media of pellets stimulated by IL-1α (r=0.87), but not in those stimulated by IGF-Iα (r=0.43). The results suggest that the concentration of antigenic KS reacting to 1/14/16H9 mirrors the GAG concentration during the stage of cartilage catabolism, but not during the cartilage anabolic stage. The concentration of antigenic KS reacting to 1/14/16H9 antibody in biological fluids could therefore be a useful marker to further understand principally the catabolic and slightly the anabolic process of articular cartilage metabolism.-KEY WORDS: cartilage metabolism, chondrocyte, equine, joint, keratan sulphate.

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“…KS and its specific roles in tumours, spinal cord and brain Analysis of GAGs associated with normal and tumour tissues and tumour cells 15,[44][45][46][47][48][49][50][51][52][53][54] and their secretions 48,55 has identified the glycan signatures of pathologic tumourogenic tissues and shown these are of diagnostic and prognostic value 15,56 . Changes in the PG compositions associated with tumour masses have also been identified 57,58 .…”

Section: Keratan Sulphate Complexity In Healthy and Diseased Tissuesmentioning

confidence: 99%

Keratan Sulphate in the Tumour Environment

Hayes

Melrose

2020

Advances in Experimental Medicine and Biology

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Keratan sulphate (KS) is a bioactive glycosaminoglycan (GAG) of some complexity composed of the repeat disaccharide D-galactose 1→4 glycosidically linked to N-acetyl glucosamine. During the biosynthesis of KS a family of glycosyl transferase and sulphotransferase enzymes act sequentially and in a co-ordinated fashion to add D-galactose (D-Gal) then N-acetyl glucosamine (GlcNAc) to an GlcNAc acceptor residue at the reducing terminus of a nascent KS chain to effect chain elongation. D-Gal and GlcNAc can both undergo sulphation at C6 but this occurs more frequently on GlcNAc than D-Gal. Sulphation along the developing KS chain is not uniform and contains regions of variable length where no sulphation occurs, regions which are monosulphated mainly on GlcNAc and further regions of high sulphation where both of the repeat disaccharides are sulphated. Each of these respective regions in the KS chain can be of variable length leading to KS complexity in terms of chain length and charge localization along the KS chain. Like other GAGs it is these variably sulphated regions in KS which define its interactive properties with ligands such as growth factors, morphogens and cytokines and which determine the functional properties of tissues containing KS. Further adding to KS complexity is the identification of three different linkage structures in KS to Asparagine (N-linked) or to Threonine or Serine residues (O-linked) in proteoglycan core proteins which has allowed the categorization of KS into 3 types, namely KS-I (corneal KS, Nlinked), KS-II (skeletal KS, O-linked) or KS-III (brain KS, O-linked). KS-I to III are also subject to variable addition of L-fucose and sialic acid groups. Furthermore, the GlcNAc residues of some members of the mucin-like glycoprotein family can also act as acceptor molecules for the addition of D-Gal and GlcNAc residues which can also be sulphated leading to small low sulphation glycoforms of KS. These differ from the more heavily sulphated KS chains found on proteoglycans. Like other GAGs, KS has evolved molecular recognition and information transfer properties over hundreds of millions of years of vertebrate and invertebrate evolution which equips them with cell mediatory properties in normal cellular processes and in aberrant pathological situations such as in tumourogenesis. Two KS-proteoglycans in particular, podocalyxcin and lumican are cell membrane, intracellular or stromal tissue associated components with roles in the promotion or regulation of tumour development, mucin-like KS-glycoproteins may also contribute to tumourogenesis. A greater understanding of the biology of KS may allow better methodology to be developed to more effectively combat tumourogenic processes.

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Keratan sulfate levels in sera of patients bearing cartilage tumors

Cited by 11 publications

References 11 publications

Reconstruction of Tissue-Specific Metabolic Networks Using CORDA

Reconstruction of Tissue-Specific Metabolic Networks Using CORDA

Consideration of the Role of Antigenic Keratan Sulphate Reacting to a 1/14/16H9 Antibody as a Molecular Marker to Monitor Cartilage Metabolism in Horses

Keratan Sulphate in the Tumour Environment

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