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 morphologic events and macromolecular interactions in matrix-induced bone formation are comparable with those occurring in the development of fracture callus. Thus, bone induction by decalcified bone matrix is an experimental model for fracture healing and a new tool for research concerning the biochemistry of bone cell differentiation. Three conditions are necessary for bone cell differentiation in postnatal life: (1) a three-dimensional pattern of proliferation of mesenchymal cells; (2) anchorage-dependent microvilli extending the proliferating cells; and (3) a locally released bone morphogenetic protein (BMP). To date, BMP with a molecular weight of 17,500-18,500 daltons has been isolated from bone, and a BMP-like protein with a molecular weight of 22,000 daltons has been extracted from mouse osteosarcoma. It is difficult to separate BMP, a collagenase-resistant, trypsin-labile acidic polypeptide, from several other low molecular weight proteins.
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PMID:Postnatal new bone formation. 670 31

1. The addition of 50 000g cytosol preparations of isolated human platelets, cultured rat osteogenic sarcoma or cultured bone cells to particulate preparations of adenylate cyclase, from the same or unrelated tissues, caused marked enhancement of the hormone-stimulated enzyme activities. 2. The degree of enhancement obtained by addition of the cytosol preparations was similar to that observed on addition of GTP. 3. The enhancing activity of the three cytosol types was found to be sensitive to digestion by trypsin and alkaline phosphatase, partially heat-labile and partially inactivated by exposure to charcoal. 4. Gel filtration studies indicated an apparent molecular weight of 20 000--30 000. Further, the 20000-30000-mol.wt. fractions obtained by gel filtration could enhance the adenylate cyclase activity of particulate preparations derived from unrelated cell types. 5. The results suggest a common or similar adenylate-cyclase-enhancing factor or factors, protein in nature, present in the three cytosol types.
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PMID:Properties of a factor in cytosol that enhances hormones-stimulated adenylate cyclase activity. 693 Sep 68

Certain metabolic properties of hormonally responsive osteogenic sarcoma cells derived from a transplantable rat tumor have been compared with those of related normal rat bone cells. All studies were carried out on cells grown in monolayer culture. Normal rat bone cells derived by repeated collagenase/trypsin digestion of newborn rat calvaria. Bone cells selected for comparison were thought to be osteoblast-like, as judged by enrichment of alkaline phosphatase and adenylate cyclase responsiveness to parathyroid hormone and prostaglandin E2. The adenylate cyclases of the two cell strains were similarly stimulated by a range of prostanoids and their metabolites and analogs. Morphology showed the two cell strains to be similar; the only obvious difference was a multilayering of cells in the sarcoma cultures, while the normal cultures showed abundant extracellular fibril formation which was not seen in the tumor cells. Investigation of the cAMP-dependent protein kinase isoenzymes showed the presence of two forms in both cell types, one eluting at a low salt concentration and the other at a high salt concentration. There was approximately twice the amount of the first isoenzyme compared to the second isoenzyme. The results indicate the usefulness of the two cell strains to elucidate further the molecular mechanisms of action of parathyroid hormone and prostaglandins.
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PMID:Functional properties of hormonally responsive cultured normal and malignant rat osteoblastic cells. 693 60

The promotive effects of poly-cations on immunoglobulin production was investigated using human-human hybridoma cells. Among poly-cations tested, epsilon-poly-L-lysine with hydrochloride (approximately 4 kDa), which has been used as an antibacterial food additive, had the greatest activity in enhancing IgM production of human-human hybridoma HB4C5 cells without stimulating cell proliferation. Immunoglobulin production stimulatory (IPS) activity of epsilon-poly-lysine was not affected by trypsin digestion. It was stable below 60 degrees C but completely inactivated with heating at 100 degrees C for 30 min. epsilon-Poly-lysine also enhanced interferon-beta (IFN-beta) production of human osteosarcoma MG-63 cells, but this stimulatory effect was reduced by the trypsin digestion.
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PMID:Enhancement of production of IgM and interferon-beta in human cell lines by poly-lysine. 853 72

Oncogenic osteomalacia is a condition where renal phosphate wasting occurs causing defective mineralisation, in the presence of a tumor. Cultures of cells were established from a hemangiopericytoma resected from a patient with oncogenic osteomalacia. Conditioned media from the cells inhibited phosphate uptake in opossum kidney cells and stimulated of cAMP in rat osteosarcoma cells, a standard parathyroid hormone (PTH)-like assay. This cAMP stimulation was suppressed by the PTH analogue, 3-34 bPTH and also by heat and trypsin treatment of the media. Tests of conditioned media for PTH and parathyroid hormone related protein (PTHrP) immunoreactivity were negative, however, and no hybridisation to probes for PTH, PTHrP or human stanniocalcin was detected in tumor cell RNA on Northern blot. These data support the hypothesis that tumors responsible for oncogenic osteomalacia produce a humoral substance that reduces renal phosphate reabsorption and provide evidence that the factor may act via PTH/PTHrP receptors.
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PMID:Characteristics of tumor cell bioactivity in oncogenic osteomalacia. 902 20

Savignygrin, a platelet aggregation inhibitor that possesses the RGD integrin recognition motif, has been purified from the soft tick Ornithodoros savignyi. Two isoforms with similar biological activities differ because of R52G and N60G in their amino acid sequences, indicating a recent gene duplication event. Platelet aggregation induced by ADP (IC50, 130 nm), collagen, the thrombin receptor-activating peptide, and epinephrine was inhibited, although platelets were activated and underwent a shape change. The binding of alpha-CD41 (P2) to platelets, the binding of purified alpha(IIb)beta3 to fibrinogen, and the adhesion of platelets to fibrinogen was inhibited, indicating a targeting of the fibrinogen receptor. In contrast, the adhesion of osteosarcoma cells that express the integrin alpha(v)beta3 to vitronectin or fibrinogen was not inhibited, indicating the specificity of savignygrin toward alpha(IIb)beta3. Savignygrin shows sequence identity to disagregin, a platelet aggregation inhibitor from the tick Ornithodoros moubata that lacks an RGD motif. The cysteine arrangement of savignygrin is similar to that of the bovine pancreatic trypsin inhibitor family of serine protease inhibitors. A homology model based on the structure of the tick anticoagulant peptide indicates that the RGD motif is presented on the substrate-binding loop of the canonical BPTI inhibitors. However, savignygrin did not inhibit the serine proteases fXa, plasmin, thrombin, or trypsin. This is the first report of a platelet aggregation inhibitor that presents the RGD motif using the Kunitz-BPTI protein fold.
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PMID:Savignygrin, a platelet aggregation inhibitor from the soft tick Ornithodoros savignyi, presents the RGD integrin recognition motif on the Kunitz-BPTI fold. 1193 56

Haematopoietic progenitor cells proliferate and develop predominantly when they adhere to bone marrow stromal cells such as osteoblasts. Therefore, changes in adhesion may be a common mechanism by which stem cells survive, mature and properly traffic between the bone marrow and the circulation. To characterize these adhesion molecules, we reduced the bone marrow cavity to a simple adhesion assay between KG1a (a CD34+ haematopoietic cell line) and osteosarcoma monolayers (MG-63 or SaOS-2). The data demonstrated that adhesion was mediated by cell-to-cell rather than cell-to-matrix contact, was sensitive to trypsin, calcium chelators and glycosylation inhibitors. Selective pretreatment attributed the constitutive binding to N-linked glycans on KG1a. When carboprocessing was inhibited later at the high mannose intermediate (via deoxymannojirimycin), adhesion was retained. Surprisingly, binding of KG1a to SaOS-2 increased past constitutive levels as doses of tunicamycin or deoxymannojirimycin dropped. Selective pretreatment suggested that this 'inducible' binding resides with molecule(s) on SaOS-2. If the terminal sialic acid was digested (via neuraminidase), this induced response was duplicated. These data, verified in primary cells, suggest that the initial tethering between blood and bone cells in this model is probably due to heavily glycosylated, rapidly processed protein(s) on both cell types.
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PMID:N-linked sialyated sugar receptors support haematopoietic cell-osteoblast adhesions. 1498 5

Human osteosarcoma MG-63 cells were induced into differentiation by 5 mmol/L hexamethylene bisacetamide (HMBA). Their nuclear matrix proteins (NMPs) were selectively extracted and subjected to two-dimensional gel electrophoresis analysis. The results of protein patterns were analyzed by Melanie software. The spots of differentially expressed NMPs were excised and subjected to in situ digestion with trypsin. The maps of peptide mass fingerprinting were obtained by MALDI-TOF-MS analysis, and were submitted for NCBI database searches by Mascot tool. There were twelve spots changed remarkably during the differentiation induced by HMBA, nine of which were identified. The roles of the regulated proteins during the MG-63 differentiation were analyzed. This study suggests that the induced differentiation of cancer cells is accompanied by the changes of NMPs, and confirms the presence of some specific NMPs related to the cancer cell proliferation and differentiation. The changed NMPs are potential markers for cancer diagnosis or targets for cancer therapy.
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PMID:Changes of nuclear matrix proteins following the differentiation of human osteosarcoma MG-63 cells. 1668 97

Bulk studies are not suitable to describe and study cell-to-cell variation, which is of high importance in biological processes such as embryogenesis, tissue differentiation, and disease. Previously, capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) was used to measure the properties of organelles isolated from millions of cells. As such, these bulk measurements reported average properties for the organelles of cell populations. Similar measurements for organelles released from single cells would be highly relevant to describe the subcellular variations among cells. Toward this goal, here we introduce an approach to analyze the mitochondria released from single mammalian cells. Osteosarcoma 143B cells are labeled with either the fluorescent mitochondrion-specific 10-N-nonyl acridine orange (NAO) or via expression of the fluorescent protein DsRed2. Subsequently, a single cell is introduced into the CE-LIF capillary where the organelles are released by a combined treatment of digitonin and trypsin. After this treatment, an electric field is applied and the released organelles electromigrate toward the LIF detector. From an electropherogram, the number of detected events per cell, their individual electrophoretic mobilities, and their individual fluorescence intensities are calculated. The results obtained from DsRed2 labeling, which is retained in intact mitochondria, and NAO labeling, which labels all mitochondria, are the basis for discussion of the strengths and limitations of this single-cell approach.
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PMID:Analysis of mitochondria isolated from single cells. 1693 92

The human osteosarcoma U2OS cell line is one of the first generated cell lines and is used in various areas of biomedical research. Knowledge of its protein expression is limited and no comprehensive study on the proteome of this cell line has been reported to date. Proteomics technology was used in order to analyse the proteins of the U2OS cell line. Total protein extracts were separated by two-dimensional gel electrophoresis (2-DE) and analysed by matrix-assisted laser desorption ionisation-mass spectrometry (MALDI-MS) and MALDI--MS-MS following in-gel digestion with trypsin and, finally, protein identification was carried out by peptide mass fingerprint (PMF) and post source decay (PSD), respectively. Approximately 3,000 spots were excised from two 2-DE gels and were analysed, resulting in the identification of 237 different gene products. The majority of the identified proteins were enzymes, regulatory proteins and RNA-associated proteins, while leukocyte markers and oncogenes were also present. Our findings include 11 protooncogenes (FKBP4, SRC8, PSD10, FUBP1, PARK7, NPM, PDIA1, OXRP, SET, TCTP and GRP75) related to the cancerous state of the U2OS cell line. The U2OS 2-DE database provides the basis for future protein studies.
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PMID:The proteome profile of the human osteosarcoma U2OS cell line. 1835 81


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