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

The rat osteosarcoma cell line UMR-106-01 has an osteoblast-like phenotype. When grown in monolayer culture, these cells transport Pi via a Na(+)-dependent carrier. The Na(+)-Pi cotransport system is stimulated by parathyroid hormone (PTH). Because there are insulin receptors on osteoblast-like cells, we determined possible effects of insulin on Na(+)-Pi cotransport in UMR-106-01 cells. Incubation of cells with 10(-8) M insulin for 3 h produced a 73% increase (P less than 0.025) in Na(+)-Pi cotransport. There was no significant change in Na(+)-L-alanine cotransport or in Na(+)-independent uptake of Pi and alanine. The stimulatory action of insulin on Na(+)-Pi cotransport was present within 2 h and was dose dependent in the range 10(-10) to 10(-7) M. The increase in Na(+)-Pi cotransport was accompanied by an increase in apparent maximal velocity with no change in apparent Michaelis constant for Pi. Use of cycloheximide to block de novo protein synthesis did not interfere with this action of insulin. We conclude that insulin, like PTH, directly stimulates the Na(+)-Pi cotransport system in osteoblast-like cells. The mechanism remains to be determined.
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PMID:Insulin stimulates sodium-dependent phosphate transport by osteoblast-like cells. 203 31

Pretreatment of the osteogenic sarcoma cell line UMR-106-01 with insulin results in sensitization to both parathyroid hormone (PTH) and isoproterenol. In insulin-pretreated cells, the two hormones cause a significantly greater cyclic AMP (cAMP) accumulation than in noninsulin-treated cells. In the presence of cholera toxin, which enhances cAMP production by these cells in both the basal and PTH-stimulated state, the effect of insulin is maintained. In the presence of pertussis toxin, which has no effect on basal cAMP accumulation but enhances both PTH and isoproterenol stimulation, insulin sensitization for both hormones is abolished. These data suggest that insulin sensitizes these cells to subsequent hormone stimulation by lessening the action of an inhibitory guanine nucleotide regulatory protein, possibly Gi.
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PMID:Insulin sensitizes a cultured rat osteogenic sarcoma cell line to hormones which activate adenylate cyclase. 216 43

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

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

We examined several characteristics of the mitogenic activity of extracts of human prostatic adenocarcinoma and human benign prostatic hyperplasia in fetal rat calvarial cells, cloned rat osteosarcoma cells and rat skin fibroblasts. Prostatic moieties produced maximal stimulation of [3H]thymidine incorporation at 24 h, were mitogenic in the absence or presence of various concentrations of serum, and were active in calvarial cells enriched with osteoblasts, skin fibroblasts and the cloned rat osteosarcoma cell line UMR 108. The known growth-promoting agents insulin, insulin-like growth factor, fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, interleukin-1 alpha and beta and transforming growth factor beta were also mitogenic in the indicator systems employed; however, maximally stimulating effects of these peptides in cells of the osteoblast phenotype were further enhanced with prostatic material. Prostatic activity was acid-stable and could be enriched with respect to osteoblast stimulation by hydrophobic and carboxymethyl ion-exchange chromatography. The results demonstrate the presence of potent mitogenic activity in hyperplastic and malignant prostatic tissue which appears to include unique osteoblast-stimulating activity.
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PMID:Effects of human prostatic mitogens on rat bone cells and fibroblasts. 245 Sep 42

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

The rat osteogenic sarcoma subclone UMR-106-01 is a cell type with osteoblast-like properties. This cell line has been shown to process specific receptors for insulin and insulin-like growth factor I (IGF-I), but not IGF-II. Insulin at physiological concentrations (1-5 ng/ml) in serum-free medium can maintain cell growth, as assessed by protein accumulation, thymidine uptake, and an increase in cell number. IGF-I is less potent than insulin, but, based on relative binding affinities for the insulin receptor, possibly acts via its own receptor. Insulin also enhances PTH-stimulated cAMP accumulation in these cells both by increasing cell number and an effect independent of cell number. Insulin may have a role in bone homeostasis.
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PMID:Insulin promotes growth of the cultured rat osteosarcoma cell line UMR-106-01: an osteoblast-like cell. 253 16

We have previously shown that insulin-like growth factor II (IGF-II) is produced by bone cells and that IGF-II stimulates cell proliferation and collagen synthesis in bone cells. We now extend these in vitro findings by demonstrating specific IGF-II binding to bone cells derived from newborn mouse calvaria and embryonic chick calvaria. The kinetics of [125I] IGF-II binding in embryonic chick calvaria cells showed time and temperature dependence. Scatchard analysis of [125I]IGF-II binding to chick calvaria cells showed an apparent Kd of 1.4 x 10(-10) M, with a calculated receptor site concentration of 40,000/cell. The specificity characteristics showed that IGF-II was significantly more potent than IGF-I or insulin in displacing IGF-II tracer. Competition for binding of [125I]IGF-II by unlabeled IGF-II showed a dose-dependent displacement between 0.5 and 25 ng/ml. Fifty percent displacement of [125I]IGF-II binding to chick and mouse calvarial cells was achieved at 1-2 ng/ml; 90% of specific binding of [125I]IGF-II was displaceable in the presence of 125 ng/ml of unlabeled IGF-II. IGF-I showed less than 5% cross reactivity for displacement of [125I]IGF-II binding to chick and mouse bone cells. Type II receptor inhibitory antibodies, R-II-PAB1 inhibited the binding of [125I]IGF-II to mouse bone cells and H-35 rat hepatoma cells (which contain type II but not type I receptors) in a dose-dependent manner. R-II-PAB1 also inhibited basal cell proliferation as well as IGF-II-, IGF-I-, and fibroblast growth factor (FGF)-induced cell proliferation in mouse bone cells. In chick calvaria bone cells and TE89 human osteosarcoma cells, R-II-PABI inhibited neither binding of [125I]IGF-II nor IGF-II-induced cell proliferation. These results together with our findings that IGF-II increased chick bone cell proliferation in the presence of maximal doses of IGF-I suggest that at least part of the mitogenic action of IGF-II is mediated through type II rather than type I receptors in bone cells.
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PMID:Characterization of the receptor for insulin-like growth factor II in bone cells. 254 14

Postmenopausal women lose bone mineral density and this loss can be prevented by estrogen administration. Although the skeletal effects of estrogens have been regarded previously as indirect, estrogen receptors have been discovered in cultured human osteoblasts and related cell lines. The UMR106 cell line derived from a rat osteogenic osteosarcoma is such an osteoblast model. We have shown direct effects of estradiol (E) on these cells in vitro, inhibiting growth and stimulating alkaline phosphatase activity (AP) corrected for cell number. This response was maximal at E conc. of 10(-10) M in serum and Phenol Red free medium, was metabolite specific and cell cycle-dependent. These cells contain high affinity binding sites with a Kd of 0.5 nM. Estrogen receptors were detected by the monoclonal antibody H-222 on Western blot after initial immunoprecipitation to concentrate the proteins. E treatment increased several enzymes including creatine kinase and LDH isoenzymes along with increments in intracellular transferrin. Transforming growth factor-beta is secreted by these cells. Secretion of this peptide was stimulated by E. TGF-beta mediated the transient growth inhibition associated with E treatment. Insulin like growth factors (IGF) are also secreted by these cells with IGF-II concentrations in the culture medium being eight times higher than IGF-I levels. E treatment increased the concentrations of both IGFs in the culture medium after a 3 day incubation. Exposure of E treated cells manifested a mitogenic response and reduced AP, indicating that E induced receptors for IGFs. These findings establish direct effects of E on osteoblastic cells in vitro and demonstrate responses to E at many levels. These osteoblast responses in vitro suggest an important role for sex steroids in the development and function of the osteoblast lineage.
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PMID:Estrogens and the skeleton: cellular and molecular mechanisms. 262 18

The calcium and phospholipid-dependent protein kinase C (PKC) system appears to play an important role in mediating hormonal effects in various tissues including bone. Accordingly, we characterized PKC activity in the UMR-106-01 rat osteosarcoma osteoblastlike cell line and examined its hormonal regulation. UMR-106-01 cells were found to possess a classic, phorbol ester-activated PKC system, which was highly calcium and phospholipid dependent. A 30 s exposure to 10 nM bovine parathyroid hormone (PTH) (1-34) increased cytosolic and membrane-bound PKC activity by 12 and 157%, respectively, resulting in a 2.2-fold increase in the membrane-bound to cytosolic (MB/C) activity ratio (all p less than 0.01). The MB/C activity ratio was highest at 20 min, exhibiting a 2.8-fold increase over the control values (p less than 0.01). In contrast, 10 nM insulin increased cytosolic PKC activity but decreased membrane-bound activity, resulting in a 61% decrease in the MB/C activity ratio at 20 min (p less than 0.02). Moreover, insulin reduced PTH stimulation of the PKC activity ratio by 42 and 62% at 30 s and 20 min, respectively (p less than 0.02). Thus, PTH and insulin have opposing effects on the PKC activity ratio in UMR-106-01 cells.
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PMID:Protein kinase C activity in UMR-106-01 cells: effects of parathyroid hormone and insulin. 268 93


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