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)

The plasminogen activator (PA) in clonal osteogenic sarcoma cells of rat origin (UMR 106-01 and UMR 106-06) and in osteoblast-rich rat calvarial cells has been characterized using specific antibodies to be tissue-type PA (tPA). An Mr value of 75,000 by SDS-polyacrylamide gel electrophoresis and fibrin autoradiography supports this characterization. There was also evidence for an Mr 105,000 component, which could be due to a proteinase-inhibitor complex. The mechanism of regulation of this tPA activity has been studied in the clonal osteogenic sarcoma cells. Parathyroid hormone (PTH) and prostaglandin E2, which increase cyclic AMP production in the sarcoma cells, also increased tPA activity. The sensitivity and magnitude of the tPA response to PTH and prostaglandin E2 were increased by simultaneous treatment with isobutylmethylxanthine (IBMX) at drug concentrations which had little effect themselves on tPA activity. In UMR 106-06 cells, which unlike UMR 106-01 cells show a cyclic AMP response to calcitonin, tPA activity was also increased in response to calcitonin, and the effect was enhanced by IBMX. 1,25-Dihydroxyvitamin D-3 also increased tPA activity in the cells, but this response was not modified by IBMX. Synthetic peptide antagonists of PTH-responsive adenylate cyclase, [34Tyr]-hPTH (3-34) amide and [34Tyr]-hPTH (5-34) amide, inhibited the PTH-induced increase in tPA activity over the same concentration range at which they inhibited cyclic AMP production, but the antagonist peptides had no effect on the tPA responses to prostaglandin E2, calcitonin or 1,25-dihydroxyvitamin D-3. These data indicate that cyclic AMP mediates the actions of PTH, prostaglandin E2 and calcitonin in increasing tPA activity in the clonal osteogenic sarcoma cells. 1,25-Dihydroxyvitamin D-3, on the other hand, increases tPA activity through a mechanism independent of cyclic AMP.
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PMID:Cyclic AMP-dependent and -independent effects on tissue-type plasminogen activator activity in osteogenic sarcoma cells; evidence from phosphodiesterase inhibition and parathyroid hormone antagonists. 301 47

To examine the role of lipid metabolism in the growth and function of osteoblast-like cells, we studied ROS 17/2.8 osteosarcoma cells and primary cultures of rat calvarial osteoblasts during growth in a serum-free medium supplemented by purified human lipoproteins or by liposomes. Increase in ROS cell number was measured in sparse (1-5 X 10(3)/cm2) cultures over 6-8 days. Liposomes (0-300 micrograms/ml) and high (HDL), low (LDL), and very low density (VLDL) lipoprotein fractions (0-300 micrograms apoprotein) markedly stimulated cell growth. Cells plated at 5 X 10(3)/cm2 achieved growth rates in the presence of LDL or HDL comparable to 10% fetal bovine serum. Serum-free culture with exogenous lipid maintained the response of cell cyclic AMP accumulation to parathyroid hormone. Cyclic AMP response to parathyroid hormone was enhanced by glucocorticosteroid, and was attenuated by 1,25-dihydroxyvitamin D (1,25(OH)2D) with an EC50 (10(-10) M) comparable to that previously observed in serum-cultured cells (J. Biol. Chem. 258:736, 1985). 1,25(OH)2D also increased the alkaline phosphatase activity in ROS cells cultured in lipid-supplemented serum-free culture. Lipoproteins or liposomes also markedly enhanced the proliferative response of sparse cultures of normal rat osteoblasts to polypeptide mitogens.
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PMID:Growth of rat osteoblast-like cells in a lipid-enriched culture medium and regulation of function by parathyroid hormone and 1,25-dihydroxyvitamin D. 322 57

Using tumour cell lines derived from human bone tumours, specific binding sites for epidermal growth factor (EGF), a potent growth stimulator in many tissues, and its effect on synthesis of prostaglandin (PG) E2, a potent bone-resorbing factor, by cultured osteosarcoma cell line were studied. Three tumour cell lines, one osteosarcoma (HOSO) and two giant cell tumours of the bone (G-1 and G-2), all possessed specific binding sites for 125I-labelled EGF: the apparent dissociation constant was approximately 4-10 X 10(-10) M and the maximal binding capacity was 50 000-80 000 sites/cell. EGF had no mitogenic effect in these cell lines. However, these cell lines did not have specific binding sites for 125I-labelled parathyroid hormone (PTH) or calcitonin. HOSO line produced and secreted PGE2 into medium, while no significant amount of PGE2 was demonstrated in G-1 or G-2 line. EGF significantly stimulated PGE2 production in HOSO line in a dose-dependent manner (0.5-50 ng/ml); its stimulatory effect was completely abolished by indomethacin, an inhibitor of PG biosynthesis. Exogenous PGE1 significantly stimulated cyclic AMP formation in HOSO line, whereas PGF2 alpha, PTH, calcitonin, or EGF had no effect. None of these calcium-regulating hormones affected cyclic AMP generation in either G-1 or G-2 line. These data indicate that human bone tumour cells have specific EGF receptors unrelated to cell growth, and suggest that EGF may be involved in bone resorption through a PGE2-mediated process in human osseous tissues.
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PMID:Specific receptors for epidermal growth factor in human bone tumour cells and its effect on synthesis of prostaglandin E2 by cultured osteosarcoma cell line. 609 85

1. The effects of several anti-prostaglandin drugs on parathyroid hormone (PTH) and prostaglandin E2 (PGE2) stimulated cyclic AMP production in freshly isolated rat osteogenic sarcoma cells have been studied. 2. PG biosynthesis inhibitors (aspirin and indomethacin) did not inhibit the effect of PTH and arachidonic acid did not enhance PTH responsiveness. 3. The PG antagonists (SC-19220, phloretin phosphate polymers, 7-oxa-13-prostynoic acid) all inhibited PGE2-stimulated c-AMP production whilst only the phloretin phosphate polymers at high concentrations inhibited the PTH effect. 4. The data suggest that the primary action of PTH and PGE2 on these bone-derived cells is independent and that a PG is not involved in the initial event in PTH action.
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PMID:Rat osteogenic sarcoma cells: modulation of hormone stimulated cyclic AMP production by prostaglandin antagonists and biosynthesis inhibitors. 610 68

The effect of parathyroid hormone (PTH 1-34 bovine) on alkaline phosphatase activity was investigated in an osteoblast-like clonal cell line derived from rat osteosarcoma (ROS 17/2). ROS 17/2 alkaline phosphatase resembled the bone enzyme in levamisole sensitivity and electrophoretic mobility but differed in heat stability. The specific activity of ROS 17/2 alkaline phosphatase increased with time in culture. This increase was inhibited by PTH (1-34) and (-)-isoproterenol in a dose-dependent manner starting at near-physiological hormone concentrations. The ID50 values were 0.02 nM for PTH (1-34) and 1.7 nM for isoproterenol. The two hormones stimulated ROS 17/2 adenylate cyclase, albeit at higher concentrations: Km values were 13 nM for PTH (1-34) and 16 nM for isoproterenol. The rise in alkaline phosphatase was also inhibited by dibutyryl cyclic AMP and 8-bromocyclic AMP (0.1 mM). These findings further document the osteoblastic properties of the ROS 17/2 osteosarcoma cell line, suggest that PTH inhibition of alkaline phosphatase represents a physiological response to the hormone in these cells, and implicate cyclic AMP as a mediator of this PTH effect.
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PMID:Alkaline phosphatase inhibition by parathyroid hormone and isoproterenol in a clonal rat osteosarcoma cell line. Possible mediation by cyclic AMP. 627 55

Although the primary cell type in human osteosarcoma is usually a neoplastic osteoblast, numerous other mesenchymal cell types may coexist in the same tumor. Previously described cloned, long-term osteosarcoma cell lines have had an osteoblastic phenotype. In this report, we describe a nonosteoblastic, long-term cell line derived from an osteosarcoma in a patient with Paget's disease. The cell line (FM-2) is nontransformed in having a low saturation density and anchorage-dependent growth, and it is nontumorigenic in nude mice. Important features of its fine structure include numerous elongated mitochondria, abundant Golgi and lysosomes, and a poorly developed rough endoplasmic reticulum. The line has high levels of lysosomal enzymes (acid phosphatase and N-acetylglucosaminidase) and low levels of alkaline phosphatase. It lacks numerous macrophage markers (lysozyme, C3, Fc receptors, and M1 antigen). The FM-2 line had a dose-dependent cyclic AMP response (7-fold increase) following treatment with calcitonin but not with parathormone. In 125I-calcitonin-binding experiments, we calculated approximately 5.3 +/- 0.2 X 10(3) receptor sites/cell with a kd of 1.8 +/- 0.1 X 10(-9) M. Conditioned medium from the FM-2 line was a potent stimulator of calcium release as assayed in a 45Ca-labeled fetal rat bone organ culture. This activity was not prostaglandin, vitamin D, parathormone, or epidermal growth factor, which are known stimulators of bone resorption. The FM-2 line does not appear to be derived from an osteoblast, macrophage, or fibroblast and may represent a calcitonin-responsive bone stem cell.
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PMID:Characteristics of a calcitonin-responsive cell line derived from a human osteosarcoma. 657 18

The hormonal metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), exerts its biological effects by initially binding to a cytosolic receptor protein. Such a protein has been demonstrated in the target organs of vitamin D3 including bone. Although the role of 1,25(OH)2D3 on the skeleton has been extensively studied in normal bone, nothing is known about its effects, if any, in abnormal bone growth. Rat osteogenic sarcoma is a useful model for bone malignancy. Tumor cells retain differentiated functions including the ability to form bone and to respond to parathyroid hormone, prostaglandins, and to a smaller extent to calcitonin with increases in cyclic AMP levels. We have here evaluated osteogenic sarcoma cell lines for the presence of a receptor for 1,25(OH)2D3. We have utilized sucrose gradient sedimentation, saturation analysis, and DNA-cellulose chromatography. Cytosol preparations from these cell lines contain a 3.3 S saturable macromolecule which binds 1,25(OH)2D3 with specificity and high affinity (Kd = 2 x 10(-10) M). The sterol-macromolecule complex binds to DNA-cellulose and its elution profile from this affinity resin is similar to that of the 1,25(OH)2D3 receptor from normal rat bone. These tumor cells should serve as a useful model for studying the action of 1,25(OH)2D3 in bone and the role of this metabolite in the biology of bone malignancy.
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PMID:1,25-Dihydroxyvitamin D3 receptor-like macromolecule in rat osteogenic sarcoma cell lines. 692 75

Protein phosphorylation was compared in normal human cells and human osteogenic sarcoma cells. The phosphorylation of endogenous cellular protein substrates was measured by two independent methods, incubation of homogenized cells with [gamma-32P]ATP or labeling of intact cells with Na2H32PO4. Phosphorylated proteins were identified by SDS-polyacrylamide gel electrophoresis and autoradiography. The stained protein bands of all four osteosarcoma cell lines were nearly identical to those of the normal cells. However, each of the osteosarcoma cell lines showed autoradiographic evidence of enhanced phosphorylation in many different protein bands which was neither cyclic AMP-dependent nor a function of cellular growth rate or density. When normal and tumor cell homogenates were mixed prior to incubation with [gamma-32P]ATP, the resulting phosphoprotein patterns resembled those obtained with the tumor cells alone. In addition, a surgically derived osteogenic sarcoma was cultured and an established line obtained; another portion of the fresh tumor was immediately homogenized and used in a phosphorylation assay. The same enhanced phosphorylation pattern was obtained with the homogenized fresh tumor as with the cell line established from it. These results suggest that human osteogenic sarcoma cells are able to perform a significantly increased amount of phosphorylation of endogenous cellular protein substrates when compared to normal human cells.
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PMID:Human osteogenic sarcoma cells exhibit enhanced protein phosphorylation. 694 94

Helodermin and helospectin are peptides structurally similar to vasoactive intestinal polypeptide (VIP) which were recently isolated from the salivary gland venom of the lizard Heloderma suspectum. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been isolated from ovine hypothalamus and also shows sequence homology to VIP. A helodermin-like peptide has been detected by combined immunohistochemical and immunochemical techniques in the thyroid C-cells. In the present study, lizard helodermin was found to cause a time- and dose-dependent stimulation of cyclic AMP (cAMP) formation in neonatal mouse calvarial bones. Also, helospectin I, PACAP 27, and the C-terminally extended PACAP 38 stimulated cAMP accumulation in the mouse calvariae. The cAMP rise in response to helodermin was comparable to that induced by VIP, both in terms of potency and magnitude of the response. Helodermin, helospectin I, PACAP 27, and PACAP 38, at concentrations of 1 mumol/liter, stimulated cAMP accumulation in enzymatically isolated mouse calvarial bone cells. A significant response to all peptides was observed in both early and late released bone cells isolated from the calvariae, with low and high alkaline phosphatase activity, respectively. Helodermin and VIP stimulated cAMP accumulation in the cloned mouse calvarial osteoblastic cell line MC3T3-E1, in rat (UMR 106-01), and human (Saos-2) osteoblastic osteosarcoma cell lines, but not in the rat osteosarcoma cell line ROS 17/2.8. The effect of helodermin was synergistically and dose-dependently enhanced by forskolin (0.1 and 1 mumol/liter). These data show that bone cells, including osteoblasts, respond to several peptides of the VIP family, including helodermin, helospectin I, PACAP 27, and PACAP 38.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Helodermin, helospectin, and PACAP stimulate cyclic AMP formation in intact bone, isolated osteoblasts, and osteoblastic cell lines. 791 21

PTH is regarded conventionally as a catabolic hormone that stimulates osteoclastic resorption of bone. However, it has been known since 1932 that intermittent pulses of PTH stimulate bone formation in animals and humans. PTH independently activates two signal mechanisms: one that stimulates adenylyl cyclase and one that stimulates protein kinase C (PKC). The goal of this study was to use the 3- to 5-month-old ovariectomized (OVX) rat model to determine which of the two signal mechanisms is responsible for the anabolic action of PTH on bone. OVX triggered a large loss of trabecular bone without significantly affecting the normal slow growth of cortical bone in the distal halves of the femora. Daily injections of human hPTH(1-34) fragment (1 nmol/100 g body weight), which stimulated both adenylyl cyclase and membrane-associated PKC activity in osteoblast-like ROS 17/2 rat osteosarcoma cells, stimulated the growth of both cortical and trabecular bone in the OVX rats. Daily injections of the same dose of hPTH(1-31), which stimulated adenylyl cyclase but not PKC in ROS 17/2 cells, stimulated trabecular bone growth in the OVX rats less effectively than hPTH(1-34), but it stimulated cortical bone growth as rapidly and as dramatically as hPTH(1-34). Injections of equimolar amounts of desamino-hPTH(1-34) [N-propionyl(2-3)hPTH-amide], which stimulated PKC as strongly as hPTH(1-34) in ROS 17/2 cells but had a drastically reduced ability to stimulate adenylyl cyclase, or injections of recombinant hPTH(8-84) which stimulated PKC only in the ROS 17/2 cells, did not stimulate cortical or trabecular bone growth in the OVX animals. Thus, cyclic AMP and cyclic AMP-dependent protein kinases may be the primary mediators of the anabolic action of intermittent pulses of PTH on bone in OVX rats.
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PMID:Parathyroid hormone fragments may stimulate bone growth in ovariectomized rats by activating adenylyl cyclase. 797


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