UMLS:C0029463 - FACTA Search

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Query: UMLS:C0029463 (osteosarcoma)
16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clonal osteoblast-like cells derived from a rat osteogenic sarcoma (UMR 106-06) were shown to possess specific, high-affinity binding sites for insulin, with a receptor density of 22,000/cell. The hormone, at physiologic concentrations (1-10 ng/ml), was found to stimulate active K+ transport into these cells, the effect being mediated via the Na+-K+ pump. Alterations in insulin-receptor status by treatment of cells with glucocorticoids or exposure to subphysiologic pH was reflected in parallel changes in the sensitivity of the K+-uptake process to the hormone. We conclude that insulin can directly affect the metabolism of bone cells and that the hormone's action on transmembrane ion transport may be linked to interaction with its cell surface receptors.
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PMID:Insulin stimulation of Na+-K+ pump in clonal rat osteosarcoma cells. 244 38

Cells of the clonal rat osteogenic sarcoma cell line, UMR 106-01, were used to investigate the regulation of collagen synthesis by PTH in osteoblastic cells. Monolayer cultures of cells were labeled with [3H] proline in order to determine both collagen type and rates of production. Analysis of labeled extracellular polypeptides on sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that UMR 106-01 cells synthesized predominantly type I collagen, accounting for 45.48 +/- 2.09% of the radioactivity incorporated into total protein. After 24-h treatment with bovine PTH (1-34, 10(-8) M), collagen synthesis (i.e. collagenase-digestible protein) was decreased to 29.45 +/- 1.39% of total protein production. This decrease was first observed 12 h after addition of hormone and greatest inhibition was achieved at 24 h. The effect of PTH was dose dependent, with half-maximal inhibition of collagen synthesis occurring at 5 x 10(-10) M after 24-h treatment. In contrast, when steady state levels of mRNA for type I collagen chains were examined by Northern blot analysis, the concentration of PTH that reduced collagen synthesis by 35-45% (10(-8) M), caused a net decrease of approximately 80-96% in the number of procollagen transcripts; a small reduction in beta-actin mRNA levels was also observed. The effect of the hormone on procollagen message level was dose dependent, with significant inhibition observed at 10(-10) M PTH and, as with collagen synthesis, maximal after 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parathyroid hormone inhibits collagen synthesis at both ribonucleic acid and protein levels in rat osteogenic sarcoma cells. 246 7

Inhibitory insulin-like growth factor binding protein (In-IGF-BP) has been purified to homogeneity from medium conditioned by TE89 human osteosarcoma cells by two different methods using Sephadex G-100 gel filtration, FPLC Mono Q ion-exchange, HPLC C4 reverse-phase, HPLC CN reverse-phase, and affinity chromatographies. In-IGF-BP thus purified appeared to be homogeneous and unique by the following criteria. (i) N-terminal sequence analysis yielded a unique sequence (Asp-Glu-Ala-Ile-His-Cys-Pro-Pro-Glu-Ser-Glu-Ala-Lys-Leu-Ala). (ii) Amino acid composition of In-IGF-BP revealed marked differences with the amino acid compositions of other known BPs. (iii) In-IGF-BP exhibited a single band with a molecular mass of 25 kDa under reducing conditions on sodium dodecyl sulfate/polyacrylamide gels. IGF-I and IGF-II but not insulin displaced the binding of 125I-labeled IGF-I or 125I-labeled IGF-II binding to In-IGF-BP. In-IGF-BP inhibited basal, IGF-stimulated bone cell proliferation and serum-stimulated bone cell proliferation. Forskolin increased synthesis of In-IGF-BP in TE85 human osteosarcoma cells in a dose-dependent manner. Based on these findings, we conclude that In-IGF-BP is a protein that has a unique sequence and significant biological actions on bone cells.
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PMID:Isolation of an inhibitory insulin-like growth factor (IGF) binding protein from bone cell-conditioned medium: a potential local regulator of IGF action. 247 22

PTH-like proteins (PTHLP), which are associated with humoral hypercalcemia of malignancy, have recently been purified. Isolation of their corresponding cDNAs has revealed that they are derived from a single gene. In this report a synthetic gene encoding PTHLP-(1-141), a 141-amino acid protein corresponding to the most abundant PTHLP cDNA detected in human tumors, was expressed in bacteria and purified to homogeneity. Recombinant (r) PTHLP-(1-141) migrates with an aberrantly high mol wt on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, presumably as a result of its unusually basic pI. rPTHLP-(1-141), like PTH, induced hypercalcemia in rats, caused release of 45Ca from fetal rat bones, and stimulated the synthesis of cAMP by rat osteosarcoma cells and canine renal membrane preparations. A comparison of the abilities of rPTHLP-(1-141) and bovine PTH-(1-34) to stimulate cAMP synthesis indicated rPTHLP-(1-141) to be 5-fold more potent in the osteosarcoma assay, while nearly 30-fold less active in the renal membrane adenylate cyclase assay. Although 100-fold less potent than bovine PTH-(1-34) in promoting bone resorption, rPTHLP-(1-141) was a potent calcemic factor in vivo, inducing a rise in serum calcium from 10.4 to 14.5 mg/dl when infused into rats at 1.3 micrograms/h. These results support previous assumptions that PTHLP is the humoral factor responsible for humoral hypercalcemia of malignancy. In addition, they suggest substantial differences between PTHLP and PTH in the regulation of calcium homeostasis.
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PMID:Synthesis of a gene encoding parathyroid hormone-like protein-(1-141): purification and biological characterization of the expressed protein. 253 1

So far, the role of fibroblasts in inflammatory processes has been underestimated. We have previously shown that stimulation of fibroblasts with viruses or bacteria results in a simultaneous production of several cytokines, including interferon-beta, interleukin (IL) 6 and colony-stimulating factors. We here report that virally infected fibroblasts produce also a chemotactic factor for granulocytes. The activity is inducible not only by measles virus but also by IL 1 beta and the double-stranded RNA poly(rI).poly(rC). This factor, when purified to homogeneity, occurs as a 6-7-kDa protein doublet upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The pure protein is serologically related to a fully characterized granulocyte chemotactic peptide (GCP) from monocytes, designated IL8. Furthermore, the chemotactic factor from fibroblasts has an NH2-terminal sequence identical to that of GCP/IL8, small differences in NH2-terminal processing being observed. Finally, in addition to diploid fibroblasts, the osteosarcoma MG-63 cell line is also a producer of GCP/IL8. It can thus be concluded that GCP/IL8 can be produced by several cell types in response to infection and that fibroblasts can contribute to chemotaxis in inflammation.
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PMID:The chemotactic activity for granulocytes produced by virally infected fibroblasts is identical to monocyte-derived interleukin 8. 266 11

The properties and regulation of insulin receptors on monolayers of cultured clonal osteoblastic rat osteosarcoma UMR-106 cells and human osteosarcoma U20S cells were studied. Confluent cultures of UMR-106 cells bound lactoperoxidase-labeled, HPLC-purified [125I]A-14-monoiodinated insulin in a reversible, saturable, and specific manner. Binding was related inversely to the incubation temperature. Prolonged period of steady-state binding was achieved at all temperatures studied. Competition curves demonstrated half-maximal inhibition of [125I]insulin binding at an unlabeled insulin concentration of about 1 nM. Scatchard analysis of the binding data was curvilinear, suggesting negative cooperativity, and revealed that UMR-106 osteoblasts contained about 87,000 receptor sites per cell according to a two-site model. Bound [125I]insulin dissociated from osteoblasts with a t1/2 of about 15 minutes at 22 degrees C. The dissociation curve was multiexponential, and the addition of native insulin accelerated the dissociation of intact but not degraded [125I]insulin. Preincubation with 125 nM insulin for 1 h induced 70% loss of binding sites and reduced total insulin bound by 30%. When monolayers were treated with the lysosomotropic agent chloroquine, a 40% increase in cell-associated radioactivity that could not be dissociable in fresh buffer was observed. The use of an energy depleter, sodium fluoride, completely inhibited the effects of chloroquine. Similar results were obtained for human osteosarcoma U20S cells except that the number of receptor sites was far less than that of UMR-106 cells. Insulin increased collagen synthesis at a half-maximal concentration of 1 nM. To conclude, cultured rat and human osteoblasts possess insulin receptors that exhibit kinetic properties and specificity similar to those of other insulin target cells. Receptor-bound insulin is internalized and degraded by a chloroquine-sensitive, energy-requiring reaction. Insulin receptor on bone cells modulates the synthesis of collagen and this role may be important in bone homeostasis.
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PMID:The characterization, regulation, and function of insulin receptors on osteoblast-like clonal osteosarcoma cell line. 269 4

A photoreactive derivative of a sulfur-free bovine parathyroid hormone (PTH) analogue, [Nle8,N-epsilon-(4-azido-2-nitrophenyl)Lys13,Nle18,Tyr34]bovine PTH-(1-34)-NH2 (NAP-NlePTH), was purified from the products of the reaction of [Nle8,Nle18,Tyr34]bovine PTH-(1-34)-NH2 (NlePTH) with 4-fluoro-3-nitro-phenylazide and was used to identify binding components of the PTH receptor in clonal rat osteosarcoma cells (ROS 17/2.8). The purified analogue, NAP-NlePTH, is a fully active agonist in three different ROS 17/2.8 cell bioassays: 1) specific binding to saturable PTH receptors; 2) stimulation of cyclic AMP accumulation; and 3) inhibition of cellular alkaline phosphatase activity; this analogue gave dose response curves parallel to and 25-33% as potent as its parent molecule, NlePTH. Radioiodinated NAP-NlePTH (125I-labeled NAP-NlePTH) retained maximal receptor-binding potency. Radioligand saturation studies in intact cells showed that the Kd of PTH receptors for the photoligand was slightly less than that for 125I-labeled NlePTH (2.8 and 0.8 nM, respectively), but that the Bmax was essentially identical for both radioligands (8 fmol/10(5) cells). Photoaffinity labeling of ROS 17/2.8 cells revealed several 125I-labeled macromolecular components by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. One predominant 125I-labeled band, having an apparent Mr of 80,000 daltons (including Mr = 4,347 ligand; hereafter referred to as the Mr = 80,000 protein), was consistently demonstrated in both reducing and nonreducing conditions. Its labeling was completely inhibited by coincubation with NlePTH (10 nM) at 26-fold molar excess to the photoligand, but not by biologically inactive PTH fragments or unrelated hormone. Labeling of several other macromolecular components persisted in the presence of NlePTH (1 microM). Only the labeling of the Mr = 80,000 protein showed saturation kinetics for photoaffinity labeling; the dose of 125I-labeled NAP-NlePTH (0.8 nM) to half-saturate labeling of the Mr = 80,000 protein was close to the Kd (2.8 nM) of specific binding of the photoligand to receptors in intact ROS 17/2.8 cells. Pretreatment of the cells with NlePTH and dexamethasone led to the predicted proportional decrease or increase, respectively, in labeling of the Mr = 80,000 protein. Our data, using a highly purified photoactive derivative of PTH, having carefully defined chemical and biological properties, show a plasma membrane component of Mr = 80,000 in ROS 17/2.8 cells that possesses the affinity, binding capacity, and physiological characteristics of the PTH receptor.
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PMID:Photoaffinity labeling of parathyroid hormone receptors in clonal rat osteosarcoma cells. 283 Dec 8

The effect of volume perturbation on the interaction of Na+ and H+ with the intracellular and extracellular faces of the Na+/H+ exchanger was studied in UMR-106 cells, a rat osteosarcoma cell line. Osmotic shrinkage of the cells stimulated the activity of the Na+/H+ exchanger. Kinetic analysis of this stimulation demonstrated that in hyperosmotically stressed cells, the apparent affinities for intracellular H+ and intracellular Na+ are modified in opposite directions. While there is an increased apparent affinity for protons from 0.275 +/- 0.03 to 0.107 +/- 0.025 microM in isotonic and hypertonic conditions, respectively, the apparent affinity for intracellular Na+ decreases from 83 +/- 9 to 126 +/- 6 mM under the same conditions. Osmotic swelling induced a decreased exchanger activity which appeared to involve reduction in Vmax only without changes in the apparent affinities of either H+i or Na+i. We conclude that: 1) osmotic shrinkage and swelling modify the kinetic behavior of the Na+/H+ exchanger in different modes; 2) in hyperosmotically stressed cells, the interactions of intracellular H+ and Na+ are modified in a selective mode. The described phenomenon may serve as a general mechanism for activation of the exchanger by various stimuli.
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PMID:Selective modification of the kinetic properties of Na+/H+ exchanger by cell shrinkage and swelling. 283 92

Retinoic acid has previously been shown to alter 1-25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors in tumorigenic (ROS 17/2A, UMR 106M) and nontumorigenic (RCJ 1.20) bone-derived cells. The mechanism of this regulation is unclear. In the present series of experiments, we have investigated the mechanism of the retinoic acid-induced increase in 1,25-(OH)2D3 receptors by studying the effects of sodium butyrate on this process. In ROS 17/2A rat osteosarcoma cells, retinoic acid induced a 2-4-fold increase in 1,25-(OH)2D3 receptors in proliferating cells but only a 1.5- to 2-fold increase in nonproliferating cells. The retinoic acid-induced increase in 1,25-(OH)2D3 receptors in proliferating ROS 17/2A cells was inhibited by sodium butyrate, but sodium butyrate had no effect on the retinoic acid-induced increase in 1,25-(OH)2D3 receptors in nonproliferating cells. Pretreatment with hydroxyurea of low density cells decreased the effect of retinoic acid, and abolished the sodium butyrate inhibition, indicating that the differing effects of retinoic acid in high and low density cells are related to cell proliferation and not to cell density or time of exposure to retinoic acid. In low density UMR 106M cells, the effects of retinoic acid and sodium butyrate on the number of 1,25-(OH)2D3 receptors were similar to those in ROS 17/2A cells. However, in RCJ 1.20 cells, a nontumorigenic cell line with some of the characteristics normally attributed to osteoblasts, the effects of retinoic acid and sodium butyrate were opposite: retinoic acid caused a decrease in the number of 1,25-(OH)2D3 receptors, which was inhibited by sodium butyrate. The possibility that the different responses observed between the two osteosarcoma cell lines and the RCJ 1.20 cells constitute differences in response pattern between tumorigenic and nontumorigenic cell lines is of interest, but requires further experimentation to verify.
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PMID:The effects of sodium butyrate on the retinoic acid-induced changes in 1,25-dihydroxyvitamin D3 receptors in tumorigenic and nontumorigenic bone derived cell lines. 283 62

The interaction of Na and H ions with the extracellular and intracellular sites of the Na+/H+ exchanger of the osteosarcoma cell line UMR-106 was investigated. Na ions interact with a single, saturable extracellular transport site. H+ and amiloride appear to compete with Na+ for binding to this site. The apparent affinity for extracellular Na+ (Nao+) and amiloride was independent of intracellular H+ (Hi+), Nai+, or an outwardly directed H+ gradient. The interaction of H+ with the intracellular face of the exchanger had a sigmoidal characteristic with a Hill coefficient of approximately 2. The apparent affinity for Hi+ was independent of Nao+ between 25 and 140 mM. The apparent affinity for Hi+, but not the number of intracellular sites, increased with the increase in the outwardly directed H+ gradient across the membrane. Nai+/Ho+ exchange (reverse mode) is an electroneutral process with a Na+/H+ stoichiometry of 1. The dependence of Nai+/Ho+ exchange on Nai+ was sigmoidal, with a Hill coefficient of 2.16. Nai+ competes with Hi+ for binding to at least the transport site. The apparent affinity for Nai+ decreased with the increase in the outwardly directed H+ gradient. High Ho+ inhibited exchange activity in the reverse mode. We conclude that intracellular Na+ and H+ can activate the exchanger. The exchanger has two separate and asymmetric extracellular and intracellular transport sites. The relative apparent affinities of the internal transport site for Na+ and H+ are determined by the direction and magnitude of the H+ gradient across the membrane. Kinetic characterization of the exchanger suggests that Na+/H+ exchange is compatible with a simultaneous transport model, although a ping-pong transport model could not be excluded.
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PMID:Cytosolic pH regulation in osteoblasts. Interaction of Na+ and H+ with the extracellular and intracellular faces of the Na+/H+ exchanger. 284 58

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