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

The osteogenic sarcoma cell line UMR 106-01 exhibits heterogeneous morphology and hormone response in subconfluent monolayer cultures. In these studies we have explored the correlation between morphological profiles and patterns of cytosolic calcium [Ca2+]i response to PTH and other agonists in single UMR 106-01 cells loaded with the Ca(2+)-sensitive fluorescent indicator, fura-2. Realtime recording of [Ca2+]i revealed that PTH (10(-7) M) produced a transient [Ca2+]i rise in 19% of the cells studied. [Ca2+]i transients were also induced by prostaglandins E2 and F2 alpha, and fetal bovine serum, but with different response frequencies (20%, 12%, and 58%, respectively). Spatial resolution of changes in [Ca2+]i by video image analysis revealed that the response to PTH was more frequent in large polygonal cells with long cytoplasmic processes and less common in smaller cells growing in clusters, whereas there was no clear subtype specificity for the effects of epidermal growth factor and fetal bovine serum on [Ca2+]i. Autoradiographic analysis of cell monolayers demonstrated a higher density of PTH-binding sites on cells with cytoplasmic extensions, whereas epidermal growth factor-binding sites were largely on colony-forming cells. Thus, the [Ca2+]i response to hormonal stimulation is heterogeneous within UMR 106-01 cell populations and within single cells, and it correlates with receptor density. This suggests that osteoblastic cells respond to PTH by activation of changes in [Ca2+]i only at certain specific steps during osteoblast development or stages of the cell cycle.
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PMID:Heterogeneous intracellular free calcium responses to parathyroid hormone correlate with morphology and receptor distribution in osteogenic sarcoma cells. 131 56

Prostaglandin E2 (PGE2), PTH, and epidermal growth factor (EGF) are potent regulators of osteoblast proliferation. In UMR 106-01 rat osteosarcoma cells with osteoblast-like features, PGE2 and PTH inhibit, while EGF stimulates, mitogenesis. Both PGE2 and PTH increase intracellular cAMP levels, cytosolic calcium, and inositol phosphate turnover. In a variety of cell types, EGF mediates its effects in part via activation of receptor protein-tyrosine kinase and other protein kinases, such as protein kinase-C. The nuclear mechanisms of PGE2, PTH, and EGF regulation of osteoblast proliferation are unknown. Accordingly, we have examined the effects of these agents on mitogenesis, second messenger generation, and primary response genes, which may link second messenger activation to subsequent alterations in gene expression. Northern blot analysis of mRNA from UMR 106-01 cells treated for 3 h with 2 microM PGE2, 10 nM PTH, or 10 ng/ml EGF in the presence of cycloheximide demonstrated that all three agents induced the expression of c-fos and c-jun mRNA. In contrast, only EGF stimulated cellular proliferation and induced Egr-1 mRNA. Also, unlike PGE2 and PTH, EGF did not increase intracellular cAMP levels. c-fos mRNA was induced by treatment with 50 ng/ml tetradecanoyl phorbol acetate or by 40 ng/ml forskolin, while induction of Egr-1 mRNA was stimulated by treatment with tetradecanoyl phorbol acetate, but not forskolin. Thus, EGF signal transduction differs from that of PGE2 and PTH in UMR 106-01 osteoblast-like cells, in that EGF does not stimulate the protein kinase-A second messenger system, but causes activation of Egr-1, a primary response gene that may play a role in the mitogenic effect of EGF.
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PMID:The effects of prostaglandin E2, parathyroid hormone, and epidermal growth factor on mitogenesis, signaling, and primary response genes in UMR 106-01 osteoblast-like cells. 133 Apr 91

The frizzled (fz) locus of Drosophila encodes a protein (Fz) with a seven-transmembrane-domain profile characteristic of G-protein-coupled receptors. In Drosophila, genetic evidence suggests that Fz functions to transmit and transduce polarity signals in epidermal cells during hair and bristle development. We have isolated from a UMR 106 rat osteosarcoma cell library a cDNA (fz-1) encoding a predicted 641-residue protein (Fz-1) with 46% homology with Drosophila Fz. We also identified a second cDNA (fz-2) encoding a protein (Fz-2) of 570 amino acids that is 80% homologous with Fz-1, with divergence most evident in the extracellular domains. Southern blots of rat genomic DNA indicated that fz-1 and fz-2 represent distinct genes. Northern analysis revealed the presence of a single fz-1 mRNA (4.7 kilobases) and two fz-2 mRNAs (2.5 and 4.5 kilobases) in rat tissues. The fz-1 and fz-2 genes are widely expressed in rat tissues with the highest steady-state levels of mRNA in kidney, liver, heart, uterus, and ovary. fz-1 and -2 mRNA levels were greater in neonatal than in corresponding adult tissues. Treatment of UMR 106 cells with bone resorbing agents including parathyroid hormone, epidermal growth factor, and 1,25-dihydroxyvitamin D3 produced increases in fz-1 and -2 mRNA levels. We suggest that hormonal induction of Fz proteins in osteoblasts serves to promote intercellular signaling required for functional responses such as increased bone resorption. Fz-1 and Fz-2 may represent products of a gene family whose members serve as transducers or intercellular transmitters of signals required for normal morphogenesis and/or differentiated function in diverse tissues.
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PMID:Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues. 133 84

The human osteosarcoma cell line (OST-1-PF) can grow in protein-free Coon's modified Ham's F12 medium. Growth of the cells in protein-free medium was partially density-dependent and partially depressed by medium change. An extract and conditioned medium of OST-1-PF cells contained high mitogenic activity for BALB/c3T3 cells. The growth factor in the cells was purified and identified as a basic fibroblast growth factor (bFGF)--like factor on the basis of its elution profile on heparin-affinity chromatography and the result of immunoblotting. An unidentified factor in a conditioned medium eliciting most of the DNA synthesis-stimulating activity showed a weak affinity for heparin. Various additions, including serum and growth factors, stimulated the growth of OST-1-PF cells in protein-free medium. Of these factors, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), acidic fibroblast growth factor (aFGF) and bFGF were the most potent mitogens. High-affinity receptors of EGF and FGF were found on the surface of these cells. These results indicate that autonomous growth of OST-1-PF cells in protein-free medium is mainly controlled by an intracellular mechanism.
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PMID:Roles of various growth factors in growth of human osteosarcoma cells which can grow in protein-free medium. 158 71

A relationship between blood plasma levels of polypeptide growth factors and those of peptide and sex steroid hormones, as assayed radioimmunologically, was studied in 91 patients with bone tumors of various histology and 45 healthy donors. The levels of insulin-like growth factor (IGF-1) and somatotropic hormone were significantly higher in cases of chondrosarcoma and patients suffering osteogenic sarcoma in the late puberal period as compared to controls and cases of fibrous histiocytoma, giant-cell tumor, benign tumors and tumor-like lesions of the bone. The peak levels of IGF-1, somatotropic hormone and insulin were registered in osteogenic sarcoma patients who developed pulmonary metastases either in the course or after the completion of combined treatment. Somatostatin level was significantly lower in patients with osteogenic sarcoma aged 11-20 years as compared to healthy adolescents, the lowest level being observed in adolescents suffering osteogenic sarcoma with metastases to the lungs. No relationship was established between total testosterone level, on the one hand, and those of IGF-1 and epidermal growth factor, on the other. A reverse correlation was established between concentrations of IGF-1 and total estradiol. The role of polypeptide growth factor antagonists in combined treatment of bone sarcomas is discussed.
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PMID:[Polypeptide growth factors and their interrelation with hormones in the blood plasma of patients with primary bone tumors]. 184 44

Purified native forms of human parathyroid hormone-related peptide (PTHrp) have recently been reported to display biological activities characteristic of transforming growth factor beta (TGF-beta). The TGF-beta-like property of PTHrp may reside within the amino N-terminal PTH-receptor binding region of the polypeptide, since a synthetic analog corresponding to amino acids 1-36 of human PTHrp is as active as purified native PTHrp in bioassays specific to TGF-beta. Complete lack of structural similarity between PTHrp and TGF-beta prompted us to address the question whether copresence of the TGF-beta-like and PTH-like biological activities in the N-terminal sequence of the PTHrp molecule is a general phenomenon observable with different N-terminal PTHrp peptides of varying amino acid chain length in a variety of target cells that respond in defined ways to TGF-beta in vitro. Two forms of synthetic N-terminal human PTHrp, PTHrp-(1-34) and [Tyr40]PTHrp-(1-40), which are fully active in conventional assays for PTH/PTHrp, were tested for effects in three in vitro bioassay systems for TGF-beta: 1) stimulation, and 2) inhibition, respectively, of epidermal growth factor-dependent soft-agar colony formation of either normal rat kidney-derived fibroblasts (NRK 49F) or human lung carcinoma cells (A549); and 3) biosynthesis of metabolically labeled fibronectin in both NRK 49F cells and clonal osteoblastic rat osteosarcoma cells (ROS 17/2.8). Human TGF-beta over the dose range of 2.5-80 pM significantly stimulated or inhibited soft-agar colony formation of either NRK 49F or A549 cells, respectively, and caused a severalfold increase in biosynthetically labeled [35S]fibronectin in NRK 49F and ROS 17/2.8 cells. In contrast, none of PTHrp-(1-34), [Tyr40]PTHrp-(1-40), and synthetic human PTH-(1-34), each tested at 0.1-10 nM, displayed detectable biological activity in any of the three assay systems. In addition, covalent cross-linking of intact NRK 49F and ROS 17/2.8 cells with either [125I]TGF-beta or 125I-[Tyr40] PTHrp-(1-40) revealed the presence of several distinct affinity-labeled receptor species for TGF-beta in both cell types and the 80K PTH/PTHrp receptors in ROS 17/2.8 cells. The affinity-labeled TGF-beta receptor species were insensitive to excess PTHrp and PTH peptides, and the 80K PTH/PTHrp receptors were insensitive to excess TGF-beta, indicating that PTHrp and TGF-beta do not cross-react with respect to receptor binding for interaction with these cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:On the transforming growth factor beta-like activity of synthetic polypeptides comprising the amino-terminal sequence of human parathyroid hormone-related peptide. 199 44

The interaction of epidermal growth factor (EGF) and PTH with UMR 106 osteosarcoma cells was examined biochemically and morphologically. EGF inhibited PTH-stimulated adenylate cyclase activity in association with a reduction in PTH receptors and a decrease in the activity of the stimulatory guanyl nucleotide-binding protein (Gs). Universal inhibition of agonist-stimulated adenylate cyclase activity did not occur, inasmuch as EGF did not reduce prostaglandin E2-enhanced enzyme activity. The influence of EGF on PTH action correlated with its effect in the UMR 106 cell population of promoting entry into the cell cycle. Morphological analysis with radioautography indicated that both EGF and PTH receptors could be colocalized to certain UMR 106 cells, but that each were more abundantly distributed over discrete UMR 106 cell types. Based on the distribution of [3H]thymidine incorporation, EGF receptors were predominantly found over rapidly proliferating cells, whereas PTH receptors were most densely distributed over more quiescent cells. The results indicate that EGF and PTH receptors are localized over specific types within the heterogeneous population of UMR 106 cells and suggest that EGF may reduce PTH action in these cultures by enhancing the proliferation of progenitor cells lacking PTH receptors and reducing differentiation in this cell population, which leads to PTH receptor-enriched target cells. EGF and PTH receptors may, therefore, be useful as probes to examine both functional interactions and differentiation pathways among cells in osteoblast models in vitro and perhaps in vivo.
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PMID:Biochemical and morphological analysis of the interaction of epidermal growth factor and parathyroid hormone with UMR 106 osteosarcoma cells. 203 59

Past work described the partial purification and characterization of a novel serine protein kinase activity designated protein kinase N (PKN) that is activated by nerve growth factor (NGF) in cultured PC12 cells [Rowland et al. (1987) J. Biol. Chem. 262; 7504-7513]. We have now devised a rapid, sensitive technique for partially purifying and assaying PKN activity in cell extracts. This methodology was applied to the IARC-EW-1 osteosarcoma and several additional non-neuronal cell lines that possess NGF receptors but that lack both morphological and a variety of additional biochemical responses to NGF. In each case, NGF significantly elevated PKN activity. The assay also revealed activation of PKN activity in IARC-EW-1 cells by additional agents, including epidermal growth factor, fibroblast growth factor, phorbol ester, and a cAMP analog. Also tested were an NGF-receptor-deficient PC12 cell variant and sublines thereof into which human NGF receptors had been introduced [Hempstead et al. (1989) Science 243; 373-375]. Acquisition of the NGF receptors resulted in NGF-activatable PKN activity. These findings indicate that detection of PKN activity may serve as a sensitive means to test NGF responsiveness in cells lacking macroscopic responses to the factor and that non-neuronal cells may be useful for studying primary signaling events in the NGF mechanism of action.
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PMID:Nerve growth factor (NGF) responses by non-neuronal cells: detection by assay of a novel NGF-activated protein kinase. 215 63

The polyanionic compound suramin is currently being evaluated for antineoplastic activity. On the basis of previous in vitro studies, it has been suggested that the mechanism of action of suramin may be related to its ability to attenuate the mitogenic effects of peptide growth factors, such as platelet-derived growth factor and epidermal growth factor. We recently reported that MG-63 human osteosarcoma cells are mitogenically responsive to insulinlike growth factor I (IGF-I). We now demonstrate for the first time that suramin interferes with the interaction between IGF-I and its receptor and abolishes in vitro IGF-I-stimulated proliferation of these osteosarcoma cells. The fact that cell proliferation resumes when suramin is removed indicates that this is not a cytotoxic effect. We conclude that IGF-I should be added to the list of growth factors whose bioactivity can be attenuated by suramin and that clinical studies of suramin and its analogues are indicated in IGF-I-receptor-positive malignancies such as osteogenic sarcoma.
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PMID:Suramin blockade of insulinlike growth factor I-stimulated proliferation of human osteosarcoma cells. 216 71

The objective of this study was to establish whether human recombinant tumor necrosis factor (TNF) can significantly stimulate the proliferation of some tumor cells. Treatment with TNF had little or no effect on the growth of human tumor cells and murine NIH/3T3 cells cultured in medium with high serum concentration. Two tumor lines, SK-MEL-109 melanoma and HOS osteosarcoma cells, were adapted to grow in medium supplemented with 0.5% serum. The growth of these SK-MEL-109 cells was inhibited by TNF, but that of the HOS cells was greatly stimulated by TNF in a dose-dependent way. Treatment with 10 ng/ml of TNF resulted in a two-fold increase in the rate of cell division. This effect of TNF was also shown by measuring DNA and protein synthesis. The continuous presence of TNF was not required for its mitogenic activity on HOS cells cultured with 0.5% serum, since treatment for only one day with TNF resulted in prolonged growth stimulation. The failure of TNF to promote division of cells cultured in medium with 10% serum may possibly be explained by the presence of saturating amounts of growth factors in serum. Interferons abolished the mitogenic activity of TNF on HOS cells. Furthermore, TNF did not show synergism with insulin or epidermal growth factor in stimulating growth of these cells. The level of c-myc mRNA was increased five-fold after 30 minutes of treatment with TNF. This shows that TNF is a growth factor for HOS cells and that it induces accumulation of c-myc mRNA.
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PMID:Tumor necrosis factor stimulates proliferation of human osteosarcoma cells and accumulation of c-myc messenger RNA. 245 Aug 80


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