Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphophoryns are the major non-collagenous proteins of the mineralized matrix of rat incisor dentin. Nearly half the phosphophoryn residues are serines, and 85-90% of these are phosphorylated. Since phosphorylation may be important for phosphophoryn function, it was of interest to identify the kinase(s) responsible for catalyzing their phosphophorylation. Rat osteosarcoma (ROS) 17/2.8 osteoblast-like cells were selected as the enzyme source. Native rat incisor phosphophoryns (RIPP-I, II, III) were not substrates for any of the ROS 17/2.8 messenger-dependent kinases but were phosphorylated by membrane-associated endogenous messenger-independent kinases. These were resolved chromatographically and identified as casein kinase (CK) I and II by elution properties and immunoblotting with a CKII antibody. The CKI preferentially used RIPP-III as substrate, while CKII preferred RIPP-I and II. Heparin at 100 and 500 ng/assay and NaCl at 0.25-0.4 M inhibited phosphorylation of the RIPP by CKI and CKII in parallel. At 10 mM spermine, phosphorylation of RIPP-I and II by CKII, and of RIPP-III by CKI were inhibited, but phosphorylation of RIPP-III by CKII was enhanced. Purified sea star oocyte CKII demonstrated the same substrate specificity and spermine concentration shift as the ROS 17/2.8 CKII. These data show that osteoblast-like cells are a rich source of membrane-bound CKI and CKII activity. The different patterns of phosphorylation of RIPP-I, II, and III further show that they are distinct synthetic products of the odontoblast.
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PMID:The in vitro phosphorylation of the native rat incisor dentin phosphophoryns. 164 38

Osteoblastic cells produce a complex extracellular matrix (ECM) composed of a mixture of proteoglycans (PGs), collagens and non-collagenous proteins. The interaction of proteoglycans with matrix effector macromolecules via either their glycosaminoglycan (GAG) chains or their protein core is critical in regulating a variety of cellular events. Alterations in the structural composition of the GAG/PG component of the ECM may have important consequences on cell proliferation and/or differentiation. Human osteoblasts and two osteosarcoma cell lines, able to produce galactosaminoglycan (GalAGs) and heparan sulphate (HS)-containing proteoglycans, were treated with their main GAG chain types, and the effects on cell growth were examined. Chondroitin sulphate (CSA) and dermatan sulphate (DS) inhibited cell proliferation of all osteoblastic cell lines at high concentration (100 microg/ml). DS showed the stronger inhibitory effect, probably due to the presence of flexible IdoA residues that provide a greater variety in conformation to these macromolecules. Heparin strongly inhibited the proliferation rates of both normal osteoblasts and transformed osteoblastic cells at concentrations > or = 1 microg/ml. The presence of large amounts of IdoA-derived trisulphated disaccharides, responsible for the overall negative charge of heparin, should be considered as a critical factor for the inhibition of cell proliferation. The obtained results suggest that matrix GAGs are factors which affect cell growth of both malignant and normal cells of the osteoblastic lineage in a concentration-dependent manner. This effect is closely related to the fine chemical structure of GAGs, i.e. the presence of L-iduronic acid and the degree of sulphation.
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PMID:Effects of glycosaminoglycans on cell proliferation of normal osteoblasts and human osteosarcoma cells depend on their type and fine chemical compositions. 1608 May 37

Osteogenic differentiation is coordinated by the exposure of cells to temporal changes in a combination of growth factors and elements within the extracellular matrix (ECM). Many of the key proteins that drive these changes share the property of being dependent on ECM glycosaminoglycans (GAGs) for their activity. Here, we examined whether GAGs isolated from proliferating, differentiating and mineralizing MG-63 osteosarcoma cells differed in their physical properties, and thus in their capacities to coordinate the osteogenic cascade both in human MG-63 osteosarcoma cells and primary human mesenchymal stem cells (hMSCs). Our results show that the size distribution of GAGs, the expression of GAG-carrying proteoglycan cores and the expression of enzymes involved in their modification systematically change as MG-63 cells mature in culture. When dosed back onto cells exogenously in soluble form, GAGs regulated MG-63 survival and growth in a dose-dependent manner, but not differentiation in either cell type. In contrast, hMSCs aggregated into distinct colonies when grown on GAG-coated substrates, while MG-63 cells did not. Heparin-coated substrates improved hMSC viability without inducing aggregation. These results suggest a complex role for GAGs in coordinating the emergence of the osteoblast phenotype, and provide further evidence for the use of heparans in bone tissue repair applications.
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PMID:Glycosaminoglycan composition changes with MG-63 osteosarcoma osteogenesis in vitro and induces human mesenchymal stem cell aggregation. 1898 89

Heparin and heparan sulfate, a variety of negatively charged highly sulfated polysaccharides, can influence the biological functions of human bone morphogenetic proteins (BMPs). Notably, BMPs control numerous essential biological activities and processes, such as bone formation, bone turnover, brain development, tumor initiation, and progression. BMPs also enhance the repair of bone tissue injuries and are used in bone remodeling alongside implantable prosthetic devices. BMPs either potentiate or inhibit the growth of cancer stem cells (CSCs). This dual biological effect appears to depend upon the cell type, underlying cytogenetic and biochemical aberrations in various distinct malignancies. Similarly, heparins may modulate CSCs positively or negatively through BMPs. The primary aims of this review are to investigate whether heparin prophylaxis would likely stimulate the propagation of a chemotherapy-resistant subpopulation of CSCs and aggravate tumor response to treatment, and result in tumor expansion, tumor recurrence and metastasis. The secondary aim is to document whether such detrimental effects surpass their beneficial effects as anticoagulants in primary bone cancers such as osteosarcoma. The current state of scientific knowledge based on key published articles from the standpoint of rigidity of data and identification of data gaps is discussed.
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PMID:Can heparins stimulate bone cancer stem cells and interfere with tumorigenesis? 2508 19