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)

Collagen synthesis in rat osteosarcoma cell line 17/2 (ROS 17/2) was assessed by measuring the incorporation of [3H]proline into collagenase-digestible protein and the formation of [3H]hydroxyproline. PTH and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited collagen synthesis in ROS 17/2 cells in a time- and dose-dependent manner. PTH reduced collagen synthesis after a 3-h incubation, whereas the effect of 1,25-(OH)2D3 was somewhat slower. Maximal and half-maximal inhibition of collagen synthesis occurred at approximately 1 and 0.1 nM of each hormone, respectively. At confluency, ROS 17/2 cells synthesized 96% type I and 4% type III collagen. PTH reduced the synthesis of type I, but not type III, collagen. PTH and 1,25-(OH)2D3 also reduced procollagen mRNA levels, as determined by a dot blot hybridization assay. Thus, ROS 17/2 cells are a convenient model system for studying the hormonal regulation of collagen metabolism and gene expression in a cloned cell line with the osteoblastic phenotype.
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PMID:Hormonal regulation of collagen synthesis in a clonal rat osteosarcoma cell line. 302 31

The degrading activity for human parathyroid hormone [hPTH-(1-84)] was studied in a rat osteoblast-like osteosarcoma cell line UMR106. At 37 C,UMR106 cells degraded hPTH-(1-84) into fragments in a time-dependent manner, which was shown by a radioimmunoassay with the use of antibody recognizing the C-terminal and middle regions of PTH molecule, whereas the degradation was completely suppressed at 4 C and failed to occur in the absence of the cells. The Lineweaver-Burk plot of this degrading activity at 37 C showed a fairly good linearity and gave a Km value of 5.1 X 10(-7) M. Reverse-phase high-performance liquid chromatography (HPLC) analysis of immunoreactive PTH fragments in the medium disclosed two peaks aside from intact PTH, indicating a limited PTH-hydrolyzing activity of UMR106 cells cleaving the molecule between at least two separate positions. This study suggests the possible involvement of osteoblasts on the metabolism of intact PTH.
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PMID:Degrading activity for human parathyroid hormone [PTH-(1-84)] in rat osteoblast-like osteosarcoma cell line UMR106. 302 90

Calcitriol exposure stimulated a human osteosarcoma cell line, U2-OS, to produce a factor(s) which stimulated bone degradation in human monocyte cultures and osteoclastic bone resorption in fetal rat long bone cultures. The factor(s) was elicited by as little as 10(-10) M calcitriol. The factor is effective in stimulating peripheral blood monocytes to degrade bone, suggesting a direct effect on cellular bone breakdown. The fetal long bone assays suggest that the osteoblast-like cells produce a factor(s) which stimulates osteoclasts. This is confirmed by the fact that human calcitonin added to the long bone cultures blocks the stimulation. The effect of PTH appears to be through the production of factors which stimulate osteoblasts. The present study suggests that a similar factor(s) may be responsible for the effect of calcitriol on bone resorption.
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PMID:A link between calcitriol and bone resorption. 320 45

A novel PTH-like peptide has recently been purified and cloned from human tumors associated with the syndrome of humoral hypercalcemia of malignancy. We surveyed the expression of mRNAs encoding this peptide in normal tissues by Northern analysis. One or more low abundance hybridizing transcripts was identified in poly(A)+ RNA prepared from human keratinocytes, thyroid, bone marrow, and fibroblasts, from bovine hypothalamus, pituitary, parathyroid, adrenal cortex, and adrenal medulla, and from rat brain, stomach mucosa, and fetal but not adult liver. One or more hybridizing transcripts was also identified in poly(A)+ RNA prepared from a number of established lines, including rat pituitary (GH4), rat pheochromocytoma (PC 12), human osteosarcoma (TE-85), and human medullary carcinoma (TT) cells. Northern analysis of mRNAs from abnormal human parathyroid tissue revealed an overexpression of transcripts for the PTH-like peptide which appeared to be specific for adenomatous or autonomous glands. These findings suggest that the PTH-like peptide is expressed in a number of endocrine and nonendocrine tissues, that it is developmentally expressed in at least one tissue (fetal liver), and that the regulation of its expression is abnormal in human parathyroid adenomas.
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PMID:Expression of messenger ribonucleic acids encoding a parathyroid hormone-like peptide in normal human and animal tissues with abnormal expression in human parathyroid adenomas. 321 62

A number of factors have been proposed as potential mediators of the syndrome of humoral hypercalcemia of malignancy (HHM), but to date no firm cause-and-effect relationship has been established. We attempted to establish such a relationship by determining whether the presence or absence of adenylate cyclase-stimulating activity (ACSA) in the media of cultured tumor cells predicted the occurrence of the syndrome of HHM when these cell lines were grown in nude mice in vivo. Conditioned media from 35 human renal carcinoma cell lines were surveyed for ACSA in the PTH-sensitive rat osteosarcoma 17/2.8 cell assay. 12 lines were positive (mean, 13.7-fold stimulation, range, 3.0 to 44.0), and 23 lines were negative (mean, 1.2-fold stimulation, range, 0.9 to 1.5). We were successful in establishing five of the positive and six of the negative lines in three to five nude mice per line. Mice implanted with the positive lines uniformly became hypercalcemic (mean serum calcium, 15.8 mg/dl), whereas mice implanted with the negative lines uniformly remained normocalcemic (mean serum calcium, 9.5 mg/dl), in spite of comparable mean tumor size. Acid-urea tumor extracts from each of four hypercalcemic animals contained potent in vitro ACSA (mean, 15.9-fold stimulation), while 5/5 extracts from normocalcemic animals did not (mean, 1.4-fold stimulation). Our study demonstrates that in this model system in vitro ACSA is a reliable predictive marker for HHM in vivo. Whether the protein responsible for this activity is also the mediator of the bone resorption seen in HHM remains to be demonstrated.
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PMID:In vitro adenylate cyclase-stimulating activity predicts the occurrence of humoral hypercalcemia of malignancy in nude mice. 334 41

Three bioassays are widely employed for the measurement of PTH-like adenylate cyclase-stimulating factors (ACSFs) derived from tumors associated with humoral hypercalcemia of malignancy. These include renal cortical adenylate cyclase (RAC) assays, rat osteosarcoma (ROS) adenylate cyclase assays, and fetal bone resorption (FBR) assays. A previous study has suggested that the potency of one human tumor-derived ACSF, expressed in PTH equivalents, was 30-fold higher in the ROS assay than in the RAC assay, but no study has directly compared all three bioassays using a single PTH standard and a single ACSF preparation. We compared one partially purified ACSF preparation to a single lot of bPTH 1-34 in all three bioassays. The results indicate that the relative potency of this ACSF as compared to the PTH standard varied with the assay employed, with the ROS assay yielding a specific activity estimate 47.5-fold higher than the RAC, and the FBR 6.7-fold higher than the RAC but 7.1-fold lower than the ROS. These findings support the possibility that distinct subpopulations of PTH receptors exist on different PTH target tissues. Further, they underscore the importance of bioassay choice when estimating the specific activity of tumor-derived ACSF preparations.
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PMID:The relative potency of a human tumor-derived PTH-like adenylate cyclase-stimulating preparation in three bioassays. 345 55

Indirect evidence suggests that cells of the osteoblastic lineage may mediate augmented osteoclastic bone resorption induced by PTH. To test this suggestion, osteoclasts were disaggregated from neonatal rat long bones and incubated on slices of human femoral cortical bone. Resorption was measured by computer-assisted morphometric and stereophotogram-metric quantification of osteoclastic excavations, identified in the scanning electron microscope after culture. We compared the effect of PTH on bone resorption by osteoclasts incubated alone with the effect of the hormone on resorption by osteoclasts cocultured with osteoblastic cells. PTH had no effect on bone resorption by osteoclasts alone, but in the presence of any of three osteoblast-containing cell populations, or in the presence of cloned, hormone-responsive osteosarcoma cells, PTH caused a 2- to 4-fold increase in osteoclastic resorption. Significant stimulation was observed at 10(-4) IU/ml PTH. None of the osteoblastic cell populations caused morphologically detectable bone resorption in the absence of osteoclasts. These results indicate that PTH acts primarily on osteoblasts, which are induced by the presence of the hormone to stimulate osteoclastic bone resorption.
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PMID:Osteoblastic cells mediate osteoclastic responsiveness to parathyroid hormone. 345 14

Parathyroid hormone (PTH, less than 10(-8) M) stimulated adenylate cyclase in fibroblasts, but not epithelial cells, isolated from fetal rat lung. In contrast to osteosarcoma cells (UMR 106), the response of fibroblasts to PTH was increased by pretreatment with cortisol (less than 10(-8)-10(-7) M).
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PMID:The adenylate cyclase response to parathyroid hormone in fetal lung fibroblasts is enhanced by cortisol. 348 Jul 62

Osteoporosis is a known complication of diabetes mellitus, suggesting a role for insulin in bone homeostasis. We studied insulin receptors and insulin action in the osteoblast-like rat osteogenic sarcoma cell line ROS 17/2.8. These cells share many common features with the osteoblast, such as 1,25-dihydroxyvitamin D3 receptors, PTH receptors, and 1,25-dihydroxyvitamin D3-induced modulation of alkaline phosphatase activity and osteocalcin. Competition binding studies revealed high affinity insulin receptors, with an ED50 for insulin of 1 nM. The receptors were highly specific for insulin, with 60% inhibition of insulin binding by an antireceptor antibody, no competition by epidermal growth factor, and an ED50 of 300 nM for proinsulin. Steady state maximal insulin binding was obtained by 40 min at 37 C, and insulin degradation, as measured by trichloroacetic acid solubility, was 1%/h at 37 C. ROS cells readily internalized insulin, and under steady state binding conditions at 37 C, 56% of the cell-associated radioactivity consisted of intracellular material. Chloroquine (100 microM) inhibited intracellular processing of insulin, leading to a 300% increase in cell-associated insulin by 2 h (37 C). Photoaffinity labeling of the insulin receptor with the photosensitive analog of insulin, B2 (2-nitro-4-azidophenyl-acetyl)des-pheB1-insulin, followed by solubilization and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, revealed specific bands of 125K and 430K mol wt under reducing and nonreducing conditions, respectively. Thus, the structure of insulin receptors in ROS cells appears comparable to that of insulin receptors of known target tissues. Insulin action was also examined. Insulin did not stimulate [2-3H]deoxyglucose uptake or [1-14C]leucine incorporation into protein. In contrast, physiological concentrations of insulin inhibited alkaline phosphatase activity in nonconfluent cells. After exposure to insulin for 24 h, alkaline phosphatase activity was decreased compared to basal by 39.5% and 50% with 5 and 50 ng/ml insulin, respectively. In conclusion, ROS cells bind insulin to specific receptors that are similar to insulin receptors on other target tissues; receptors internalize insulin, which is then processed through a chloroquine-sensitive pathway; insulin does not affect membrane substrate transport; and insulin does inhibit the activity of an enzyme that is important in bone metabolism. ROS cells represent a model for studying insulin effects on bone.
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PMID:Demonstration of insulin receptors and modulation of alkaline phosphatase activity by insulin in rat osteoblastic cells. 353 Jul 24

Peptides corresponding to the amino-terminal region of the parathyroid hormone-related protein (PTHrP) of humoral hypercalcemia of malignancy were synthesized. A 34-amino acid peptide, PTHrP(1-34), was two to four times more potent than bovine or human PTH(1-34) in bioassays promoting the formation of adenosine 3',5'-monophosphate (cAMP) and plasminogen activator activity in osteogenic sarcoma cells and adenylate cyclase activity in chick kidney membranes. Like parathyroid hormone itself, in which the activity resides in the first 34 residues, PTHrP peptides of less than 30 residues from the amino terminus showed substantially reduced activity. PTHrP(1-34) had only 6% of the potency of bovine PTH(1-34) in promoting bone resorption in vitro. PTHrP(1-34) strongly promoted the excretion of cAMP and phosphorus and reduced the excretion of calcium in the isolated, perfused rat kidney consistent with the symptoms seen in malignant hypercalcemia.
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PMID:Parathyroid hormone-related protein of malignancy: active synthetic fragments. 368 95


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