Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Screening for retinoic acid-binding protein (RABP) in experimental tumors revealed the presence of this protein in three mammary tumors, two metastatic colon tumors, B16 melanoma. Lewis lung carcinoma, Ridgway osteogenic sarcoma, and keratoacanthoma. RABP was below the limits of detection in two weakly metastatic colon tumors and in Sarcoma 180. After s.c. implantation of RABP-containing tumors into mice, this protein could be traced in the lungs due to pulmonary metastasis. Following implantation of Lewis lung tumors, RABP was detected in the lung on the 6th day. On the 15th day after implantation, RABP was present in lung and brain, but not in other tissues where this protein was normally lacking. In primary cultures of Lewis lung carcinoma, the lower limit for detection of RABP by sucrose gradient sedimentation technique corresponded to 0.12 mg protein that was extractable from 3 X 10(5) cells. Both chick embryo skin and rabbit ear skin extracts contained RABP; the level of cellular retinol-binding protein was high in chick embryo skin but only marginal in rabbit ear. The amounts of these proteins on chick embryo skin and rabbit ear skin correlate with the biological potency of retinol and retinoic acid, as observed by others.
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PMID:Retinoic acid-binding protein in experimental tumors and in tissues with metastatic tumor foci. 56 58

In this study we have used a reverse transcription polymerase chain reaction (RT-PCR) to demonstrate that adult primary human osteoblasts and SaOS-2, a human osteosarcoma-derived cell line with osteoblastic properties, express cellular retinol-binding protein I (CRBP I), cellular retinoic acid-binding protein II (CRABP II), and very low levels of CRABP I. We also show that CRABP II is expressed in the adult liver, which does not express CRABP I. The results suggest that CRABP II is the important isoform in the adult bone as well as in the adult liver. Since the 9-cis retinoic acid receptor (RXR) alpha previously has been shown to be expressed predominantly in the liver, CRABP II might be involved in the transport of 9-cis retinoic acid to its nuclear receptor.
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PMID:Cellular retinoic acid-binding protein type II is expressed in adult human osteoblasts and in adult liver. 128 1

Bone metabolism is regulated by a wide variety of both circulating and locally produced peptides. The activity of such agents must be regulated, and one potential regulating mechanism is the inactivation of these peptides by locally produced proteolytic enzymes. One candidate for such a class of enzymes is enkephalinase (EC 2.3.24.11), a membrane-bound neutral metalloendopeptidase that inhibits the activity of a range of biologically active peptides, including interleukin-1 (IL-1), a potent bone-resorbing agent. In this study, we examined the effects of human enkephalinase on bone resorption in cultures of fetal rat long bones. We found that partially purified and highly purified enkephalinase inhibited bone resorption stimulated by parathyroid hormone (PTH) and IL-1 alpha. The effects on PTH-stimulated resorption were reversible, but enkephalinase did not inhibit prestimulated resorption. Enkephalinase also inhibited resorption induced by the nonpeptide stimulators 1,25-(OH)2D3, retinoic acid, and prostaglandin E2 (PGE2). In addition, preliminary studies confirmed a previous report of the presence of an enkephalinase-like activity in osteoblast-like osteosarcoma cells. These data are consistent with the hypothesis that proteolytic enzymes, such as enkephalinase, may play a role in the local regulation of bone resorption.
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PMID:Inhibition of bone resorption in vitro by human enkephalinase (EC 3.4.24.11), a neutral metalloendopeptidase. 158 28

1,25(OH)2D3 was found to regulate its own receptor levels via an increase in corresponding mRNA levels in human osteoblast-like osteosarcoma cells (MG-63). In addition, exposure of the cells for 24h to dexamethasone, estradiol, retinoic acid, or triiodothyronine resulted in a dose-dependent accumulation of hVDR mRNA. Combination of 1,25(OH)2D3 with any other hormone used in this study did not result in an additive increase in hVDR mRNA levels. Progesterone or dihydrotestosterone did not influence hVDR mRNA levels. Of the studied hormones, only 1,25(OH)2D3 was alone able to stimulate the synthesis and secretion of osteocalcin. Compared with 1,25(OH)2D3, the combination of 1,25(OH)2D3 and retinoic acid resulted an increased synthesis of osteocalcin. In contrast, the combination of 1,25(OH)2D3 with dexamethasone, estradiol, or triiodothyronine diminished the stimulatory effect of 1,25(OH)2D3. A complex interaction of several different hormone receptors seems to occur within the regulatory regions of hVDR and osteocalcin genes, or at the level of translation, resulting, in each case, a finely adjusted vitamin D receptor and osteocalcin expression.
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PMID:Hormonal regulation of vitamin D receptor levels and osteocalcin synthesis in human osteosarcoma cells. 165 30

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) act via PTH receptors in bone to stimulate bone resorption. Bone resorption is also stimulated by certain cytokines, which are produced in bone and bone marrow. The effects of such cytokines on the PTH-receptor system were studied in the osteoblast-like osteosarcoma cell line UMR 106-06. 125I-labelled PTHrP-(1-84)-peptide bound specifically to the cells, and PTHrP-(1-34) and -(1-84) competed with equimolar affinity for binding to UMR 106-06 cells. The specific binding of 125I-PTHrP-(1-84) could be completely blocked by PTH. Therefore 125I-PTHrP-(1-84) bound to a classical receptor in UMR 106-06 cells. Preincubation for 3 days with either tumour necrosis factor alpha (TNF alpha) or retinoic acid (RA) both decreased the specific binding of 125I-PTHrP-(1-84) to about 40% of control levels. These effects were specific for PTH binding, since there was little effect on 125I-salmon-calcitonin binding. Both TNF alpha and RA required 24 h exposure to cells to produce a measurable effect. The decrease in 125I-PTHrP-(1-84) binding was due to a reduced number of binding sites, with little apparent change in affinity. Half-maximal effects were seen with 1 ng of TNF alpha/ml, whereas 1 microM-RA was needed to observe the loss of PTH receptors. Combinations of RA and TNF alpha produced a greater effect than that of either agonist alone. The loss of PTH receptors was accompanied by a specific loss of PTH-stimulated cyclic AMP production. Preincubation with TNF alpha increased the basal plasminogen activator (PA) activity in the cells and decreased the amplitude of the response of PA activity to PTH compared with control cells. Furthermore TNF alpha decreased sensitivity to PTH (50% stimulation of PA activity with 0.1 nM-PTH in control cells versus 50% stimulation with 0.3 nM-PTH in TNF alpha-treated cells). In contrast, TNF alpha pretreatment increased the amplitude of the response of PA activity to calcitonin, whereas sensitivity to calcitonin was not altered. These data are consistent with a specific down-regulation of PTH receptors in osteoblast-like UMR 106-06 cells after exposure to TNF alpha or RA. The loss of PTH receptors is accompanied by a decreased responsiveness to PTH, as measured with the PA system in these cells. A loss of PTH receptors could modulate PTH responses in osteoblasts, either in the local control of bone formation and resorption, or in pathological conditions such as humoral hypercalcaemia of malignancy.
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PMID:Specific down-regulation of parathyroid hormone (PTH) receptors and responses to PTH by tumour necrosis factor alpha and retinoic acid in UMR 106-06 osteoblast-like osteosarcoma cells. 166 Jul 13

We have previously shown that osteocalcin synthesis is readily induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in MG-63 human osteosarcoma cells (Mahonen et al. (1990) Biochim. Biophys. Acta 1048, 30-37). In the present study, the regulation of osteocalcin synthesis by other hormones of the steroid-thyroid hormone family (retinoic acid, 17 beta-estradiol, triiodothyronine, and dexamethasone) was examined. We found that the other hormones alone had no effects on medium osteocalcin and osteocalcin mRNA concentrations by 96 h of treatment. Compared with 1,25(OH)2D3, however, the combination of 1,25(OH)2D3 with dexamethasone resulted in a greatly reduced medium osteocalcin concentration. Also estradiol and triiodothyronine diminished the stimulatory effect of 1,25(OH)2D3. In contrast, the combination of 1,25(OH)2D3 with retinoic acid resulted in an increased medium osteocalcin concentration. The inhibition of osteocalcin synthesis by dexamethasone and triiodothyronine was accompanied by decreased osteocalcin mRNA levels. Retinoic acid and estradiol, however, did not influence the 1,25(OH)2D3-induced osteocalcin mRNA levels. To examine the specificity of the hormonal effects, the activity of alkaline phosphatase was determined. Both baseline and 1,25(OH)2D3-stimulated alkaline phosphatase activity was found to be inhibited by all other hormones. These results suggest that the steroidal hormones specifically affect osteocalcin synthesis in osteoblastic bone cells, and that complex interactions occur at the level of transcription and/or translation resulting in each case in a finely adjusted rate of osteocalcin synthesis.
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PMID:Modulation of 1,25(OH)2D3-induced osteocalcin synthesis in human osteosarcoma cells by other steroidal hormones. 182 Sep 70

We have examined the ability of dexamethasone, retinoic acid, and vitamin D3 to induce osteogenic differentiation in rat marrow stromal cell cultures by measuring the expression of mRNAs associated with the differentiated osteoblast phenotype as well as analyzing collagen secretion and alkaline phosphatase activity. Marrow cells were cultured for 8 days in primary culture and 8 days in secondary culture, with and without 10 nM dexamethasone or 1 microM retinoic acid. Under all conditions, cultures produced high levels of osteonectin mRNA. Cells grown with dexamethasone in both primary and secondary culture contained elevated alkaline phosphatase mRNA and significant amounts of type I collagen and osteopontin mRNA. Addition of 1,25-dihydroxyvitamin D3 to these dexamethasone-treated cultures induced expression of osteocalcin mRNA and increased osteopontin mRNA. The levels of alkaline phosphatase, osteopontin, and osteocalcin mRNAs in Dex/Dex/VitD3 cultures were comparable to those of 1,25-dihydroxyvitamin D3-treated ROS 17/2.8 osteosarcoma cells. Omitting dexamethasone from either primary or secondary culture resulted in significantly less alkaline phosphatase mRNA, little osteopontin mRNA, and no osteocalcin mRNA. Retinoic acid increased alkaline phosphatase activity to a greater extent than did dexamethasone but did not have a parallel effect on the expression of alkaline phosphatase mRNA and induced neither osteopontin or osteocalcin mRNAs. In all conditions, marrow stromal cells synthesized and secreted a mixture of type I and III collagens. However, dexamethasone-treated cells also synthesized an additional collagen type, provisionally identified as type V. The synthesis and secretion of collagens type I and III was decreased by both dexamethasone and retinoic acid. Neither dexamethasone nor retinoic acid induced mRNAs associated with the chondrogenic phenotype. We conclude that dexamethasone, but not retinoic acid, promotes the expression of markers of the osteoblast phenotype in cultures of rat marrow stromal fibroblasts.
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PMID:Dexamethasone induction of osteoblast mRNAs in rat marrow stromal cell cultures. 202 91

We have examined the effects of parathyroid hormone (PTH) and PTH-related peptide (PTH-rP) on intracellular calcium (Ca2+i) in a rat osteogenic sarcoma cell line, UMR106. Synthetic bovine (b)PTH(1-34) caused a small inconsistent rise in Ca2+i in UMR106 cells, whilst cells pretreated with retinoic acid (RA, 1 mumol/l) for 18 h exhibited reproducible, significant and dose-dependent increases in Ca2+i levels in response to bPTH. The effect of RA on PTH-induced changes in Ca2+i were dependent upon both dose and time. Purified human (h)PTH-rP(1-34) increased Ca2+i in the absence of RA in the same cells. However, RA increased the magnitude of PTH-rP-stimulated changes in Ca2+i without affecting the concentration required for a maximal response. RA also prolonged the delay before the Ca2+i response was observed. Maximal responses to PTH-rP were greater in magnitude than those to PTH. These changes appeared not to be due to cyclic AMP (cAMP), since neither dibutyryl cAMP (1 mmol/l) nor forskolin (15 mumol/l) affected Ca2+i. PTH- and PTH-rP-mediated Ca2+i transients were not completely abolished by the absence of extracellular calcium, and both peptides increased basal levels of inositol trisphosphate. PTH and PTH-rP were subject to mutual desensitization, but were not desensitized by prostaglandin E2. PTH(7-34) antagonized PTH- but not PTH-rP-mediated Ca2+i transients. We conclude that there may be some important differences in the mechanism of action of PTH and PTH-rP.
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PMID:The effect of retinoic acid on parathyroid hormone- and parathyroid hormone-related peptide-induced intracellular calcium in a rat osteosarcoma cell line, UMR106. 203 Mar 32

Specific binding of leukemia-inhibitory factor (LIF) to osteoblasts, but not multinucleated osteoclasts, was demonstrated by receptor autoradiography by using cells isolated from newborn rat long bones. The clonal rat osteogenic sarcoma cells, UMR 106-06, which have several phenotypic properties of osteoblasts, expressed 300 LIF receptors per cell, with an apparent KD of 60 pM. Treatment of calvarial osteoblasts or UMR 106-01 cells with LIF resulted in a dose-dependent inhibition of plasminogen activator (PA) activity. Both calvarial osteoblasts and osteogenic sarcoma cells were shown by Western blotting and reverse fibrin autography to produce plasminogen activator inhibitor-1 (PAI-1), the production of which was increased by LIF treatment. Northern blot analysis revealed that LIF treatment resulted in a rapid (peak 1 hour), dose-dependent increase in mRNA for PAI-1. LIF treatment of the preosteoblast cell line, UMR 201, enhanced the alkaline phosphatase response of these cells to retinoic acid. Each of the osteoblast-like cell types (calvarial osteoblasts, UMR 106-06, and UMR 201) was shown to produce LIF by bioassay and, by using the polymerase chain reaction (PCR), was shown to express low levels of mRNA for LIF. These data establish that cells of the osteoblast lineage are targets for LIF action. The reported anabolic effects of this cytokine on bone formation in vivo could be related to inhibition of protease activity. LIF may be an important paracrine modulator in bone, or perhaps an autocrine one, based on the evidence for its production by osteoblasts and osteoblast-like cells.
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PMID:Osteoblasts display receptors for and responses to leukemia-inhibitory factor. 217 Apr 27

Introduction of an exogenous retinoblastoma (RB) gene in RB-deficient retinoblastoma or osteosarcoma cells has been shown to suppress their neoplastic phenotype. In experiments designed to explore the potential mechanism of RB tumor suppression, we report here that the phosphorylation state of RB protein is modulated during normal cellular events. In resting cells, RB protein is present in its least phosphorylated form; in rapidly proliferating cells, RB protein is highly phosphorylated. Maximal phosphorylation is associated with S phase of the cell cycle. Induction of differentiation in several human leukemia cell lines by treatment with phorbol ester or retinoic acid leads to dephosphorylation of RB. Time course studies indicate that RB dephosphorylation precedes the total arrest of cell growth during differentiation. These observations strongly suggest that the function of RB protein is modulated by a phosphorylation/dephosphorylation mechanism during cell proliferation and differentiation.
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PMID:Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation. 267 46


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