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)

This study examines the osteoblastic properties of the established human osteosarcoma cell line Saos-2. Saos-2 cells inoculated into diffusion chambers, which were implanted i.p. into nude mice, produced mineralized matrix in 4 of 6 chambers at 8 weeks. In 5 of 6 chambers there was a strong positive alkaline phosphatase reaction. In culture the alkaline phosphatase levels increased with time and cell density, reaching very high levels at confluence: 4-7 mumol/mg protein/min. The cells show a sensitive adenylate cyclase response to parathyroid hormone, 50% effective dose = 2.8 nM, which increases with cell density and is further raised by dexamethasone treatment. They also exhibit typical binding of 1-25-dihydroxyvitamin D3 to 3.2S receptor protein with an apparent Kd of 0.21 nM; the numbers of sites per cell were 3,300 at 50,000 cells/cm2 and 1,800 at 280,000 cells/cm2. The presence of osteonectin was visualized with a monoclonal antibody which revealed a reticular pattern on the cell surface. Osteonectin was also detected in the medium by Western blots, migrating at around Mr 40,000 in nonreduced gels and Mr 44,000 in reduced gels. The Saos-2 cells thus possess several osteoblastic features and could be useful as a permanent line of human osteoblast-like cells and as a source of bone-related molecules.
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PMID:Characterization of a human osteosarcoma cell line (Saos-2) with osteoblastic properties. 304 Feb 34

Polyclonal antibodies against osteonectin, a 32 kd non-collagenous bone protein, were applied for the histogenetic identification of variously differentiated osteosarcoma tissues. A strong positive reaction was found in matrix-producing osteosarcoma cells of the osteoblastic type, but pleomorphic or fibrosarcomatous osteosarcoma tissues reacted focally positive as well. Because the production of osteonectin depends on the osteoblastlike function of the individual tumor cell, a homogeneous immunocytochemical staining of all tumor cells cannot be expected. Nevertheless, the immunocytochemical demonstration of osteonectin in osteolytic tumors that produce no or scarcely any matrix seems to be a valuable tool for establishment of their osteogenic origin.
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PMID:Immunohistochemical study of osteonectin in various types of osteosarcoma. 316 50

TGF beta 1 from porcine platelets increased alkaline phosphatase (AP) activity in the rat osteoblastic cell line ROS 17/2.8 about three-fold. This effect was dose-dependent with an ED50 of about approximately 0.2 ng/ml and was larger during logarithmic growth than at confluence. TGF beta 1 inhibited cell growth by about 30% with similar dose dependence. Thirty min exposure to TGF beta 1 was sufficient to increase AP activity 3 days later by about two-fold but did not affect cell growth, suggesting dissociation between effects on proliferation and differentiation. The rise in AP activity started 6 h after TGF beta 1 addition and was blocked by cycloheximide and actinomycin D. TGF beta 1 also increased AP mRNA by two- to three-fold and this effect was not blocked by cycloheximide. The half-life of AP mRNA, estimated following the addition of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole was about ten h in both control and TGF beta 1-treated cells. The mRNAs for type I procollagen and osteonectin were also increased by TGF beta 1 but fibronectin mRNA was decreased. TGF beta 2 effects on AP and cell growth were similar to those of TGF beta 1, except for lack of activity following transient exposure. At saturating concentrations, TGF beta 2 (2 ng/ml) or dexamethasone (10(-7) M), which has similar effects on these cells, did not further augment the effects of TGF beta 1 (at 2 ng/ml). Above findings suggest that TGF beta promotes osteoblastic differentiation in rat osteosarcoma cells at least in part by acting at the pretranslational level.
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PMID:Type beta transforming growth factor (TGF beta) regulation of alkaline phosphatase expression and other phenotype-related mRNAs in osteoblastic rat osteosarcoma cells. 348 Feb 88

Among the solid tumors of childhood and adolescence, osteosarcoma (OS) represents the most prominent example of efficient aggressive chemotherapy with secondary surgical therapy. A specific subclassification of the tumor is indispensable and must include recent results of cell biology. The co-distribution of different collagen types I-VI reflects the diverse differentiation of osteosarcoma cells, supporting the concept of a pluripotent mesenchymal cell to be the stem cell of the tumor. In contrast, osteonectin (SPARC) may not be considered as a reliable marker for osteosarcoma. The experience of special proteins being secreted by osteosarcoma cells is rather limited. Detailed molecular biological studies are still lacking. A loss of alleles on chromosome 17, particularly in the defined region 17p 13, can be observed in more than 75% of all OS, suggesting the contribution of a tumor suppressor gene, p53, located in that region. It is a 53 kd nucleophosphoprotein binding the major transforming protein, the large T antigen of Simian Virus 40. Immunohistological results showed positive staining with the antibody Pab 240 in 13 of 18 cases. In one osteoblastic OS, a novel splice mutation resulting in a fusing of exon 5 directly to exon 7 was detected. RB1 gene is also of major importance for the tumorigenesis of OS. The multidrug resistance (mdr) is associated with a membrane-bound channel-forming transport protein, the P-glycoprotein. It is a conserved plasma membrane component of about 170 kd. Both the human isoforms mdr 1 and mdr 3 are localised in the long arm of chromosome 7.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New aspects of cell biology in osteosarcoma. 747 79

Estrogen deficiency is well recognized as a cause of bone loss in rats and humans. Likewise, treatment with estrogen results in prevention of this loss. Initially, this effect was thought to be indirectly mediated but, more recently, estrogen receptors (ER) have been reported in osteosarcoma cells and primary cultures originating from surgical waste, suggesting a direct effect of this steroid hormone. Detection of ER in skeletal tissues, however, has remained elusive. The purpose of this investigation was to establish the efficacy of the highly sensitive reverse-transcription polymerase chain reaction (RT-PCR) technique to detect ER in a well defined skeletal tissue (calvarial periosteum) that is responsive to the hormone. Primers were made specific to rat ER sequences. Total RNA was extracted from rat uterus, liver, spleen, and the periosteum using an organic solvent method. cDNA was synthesized from 2 micrograms total RNA. cDNA corresponding to 40 ng total RNA/sample produced intense PCR products for ER. In descending order of intensity were uterus, liver, bone, and spleen. Importantly, a similar time-course for estrogen-induced down-regulation of steady-state mRNA levels for alkaline phosphatase and osteonectin was observed in calvarial periosteum and tissues known to express estrogen receptors. These data provide in vivo evidence of ER mRNA in bone and suggest that at least some of estrogen's action on bone is directly modulated.
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PMID:Estrogen receptor mRNA is expressed in vivo in rat calvarial periosteum. 748 34

Prolonged glucocorticoid treatment causes osteoporosis in vivo and inhibits bone formation in vitro. We have previously shown that glucocorticoids inhibit calcification and alter osteoblast organization in a mineralizing bone organ culture system. In this study, the effect of glucocorticoids on osteoblast adhesion to bone matrix proteins and integrin expression was examined in primary rat osteoblasts and a transformed rat osteosarcoma-derived cell line ROS 17/2.8. After 24 h of treatment with corticosterone, these cells displayed a concentration-dependent decrease in adhesion to type I collagen and fibronectin. Adhesion was significantly decreased as early as 4 h after glucocorticoid administration. With 100 nM corticosterone treatment for 24 h, inhibition of the adhesion of ROS 17/2.8 cells and primary osteoblasts to fibronectin was 75 +/- 10% and 50 +/- 8%, and inhibition of adhesion to collagen was 31 +/- 10% and 65 +/- 5%, respectively. This effect was specific for osteoblasts, because glucocorticoids did not change the adhesion of fibroblasts. However, glucocorticoids did inhibit the adhesion of all cell types to rat osteonectin. To determine whether the change in osteoblast attachment to collagen and fibronectin was due to an alteration in integrin levels, the plasma membranes of these cells were labeled with [125I]lactoperoxidase, solubilized, and immunoprecipitated with an antibody to beta 1. A 24-h treatment with 100 nM corticosterone caused 80 +/- 2% and 64 +/- 9% decreases in beta 1 levels in primary osteoblasts and ROS 17/2.8 cells, respectively. These results were confirmed with immunofluorescence microscopy, which showed a glucocorticoid-induced decrease in beta 1 staining. Treatment of primary rat osteoblasts and ROS 17/2.8 cells for 72 h with corticosterone also decreased beta 1-integrin messenger RNA levels in a dose-dependent manner. We have demonstrated that the inhibition of integrin expression by glucocorticoids is involved in the decrease in osteoblast adhesion to bone extracellular matrix proteins. These data suggest that integrin modulation may influence osteoblast function and bone formation and, thus, contribute to glucocorticoid-induced osteoporosis.
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PMID:Glucocorticoids inhibit the attachment of osteoblasts to bone extracellular matrix proteins and decrease beta 1-integrin levels. 753 Jun 48

Procollagen and proteoglycan biosynthesis was defined in long-term culture of a human osteogenic sarcoma cell line, SAOS-2. An osteoblast phenotype was maintained by these cells up to 40 days post-confluent in the presence of ascorbic acid. Under these conditions, cells deposited around them an extensive collagenous matrix that was able to mineralize in the presence of an exogenous phosphate donor (beta-glycerophosphate). The collagenous matrix was comprised predominantly of collagen type I with significant amounts of collagen type V, and greater than 80% of the collagen in the matrix was involved in covalent crosslinkages. With increasing time in culture there was a decrease in the collagen synthetic rate, although the collagenous matrix was maintained. The proteoglycans synthesized by nonmineralizing and mineralizing cultures were purified after biosynthetic labeling with [35S]sulfate and [3H]glucosamine. Two major species were apparent: a large chondroitin sulfate proteoglycan (CSPG), and a small chondroitin sulfate proteoglycan, decorin. In nonmineralizing cultures, decorin partitioned equally between the cell layer and culture medium, whereas the large CSPG species partitioned exclusively into the cell layer-associated matrix. In the presence of extensive mineral deposition, greater than 90% of the newly synthesized proteoglycans were secreted into the medium. Northern blot hybridization indicated that SAOS-2 cells express mRNA encoding a range of bone proteins, including decorin, osteonectin, and bone sialoprotein.
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PMID:Matrix deposition by a calcifying human osteogenic sarcoma cell line (SAOS-2). 760 1

To determine whether a system of ectopic bone formation induced by osteosarcoma-derived bone-inducing substance (bone morphogenetic protein-4) can be used as a model of developing bone at the molecular level, we studied the expression of bone-related protein mRNAs in the process of ectopic bone formation using non-radioisotopic in situ hybridization. Osteonectin mRNA was detected in fibroblast-like cells, which are similar to periosteal cells from the early to middle stages of bone development. The proportion of osteonectin mRNA-expressing cells was greater than that of osteopontin mRNA-expressing cells in hypertrophic chondrocytes and osteoblast-like cells. In contrast, osteopontin mRNA was localized in a limited population of hypertrophic chondrocytes, a single layer of osteoblast-like cells adjacent to the bone trabeculae in the middle stage of bone formation, and in a limited subset of osteocytes in the late stage. A strong osteocalcin mRNA signal was detected in osteoblast-like cells from the middle to late stages and in a limited subset of osteocytes in the late stage of bone development. Since the sequential gene expression pattern of bone-related proteins in the present system is comparable to that in embryonic osteogenesis, this system may be useful as a model for studying gene expression in osteogenesis.
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PMID:Expression of mRNA of murine bone-related proteins in ectopic bone induced by murine bone morphogenetic protein-4. 805 37

Cell lines were established from three spontaneous osteosarcoma and one fibrosarcoma of aging mice. They were studied for tumorigenicity, osteoblastic features, and other in vitro cellular characteristics, by a combination of histological, morphological, biochemical, and molecular approaches. It was found that all cell lines formed tumors in vivo, whereas in vitro, only the fibrosarcoma-derived cell line grew efficiently in soft agar. Three out of the four cell lines produced mouse endogenous retroviruses, but none were classical sarcoma viruses. Type I collagen was expressed by all the cell lines, as was another extracellular matrix protein, osteonectin. The osteosarcoma-derived cell lines, however, exhibited different degrees of osteogenic differentiation. Only one line (OSA), and its clonal subline (1G11), consistently gave rise to mineralized tumors after transplantation into syngeneic mice, and these cells expressed high levels of alkaline phosphatase and bone-specific osteocalcin mRNA in vitro. Expression of these biochemical markers of osteoblasts occurred to a lesser extent in a second line (OSC) and was undetectable in the third line (OSB). The clonal 1G11 cell line exhibits the phenotype of a fully mature osteoblast and thus may serve as a particularly useful model for studies of bone cell function and regulation. Studies of cells which display a wide spectrum of osteogenic potential may further our understanding of the mechanisms involved in bone cell differentiation and tumorigenicity.
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PMID:Spectrum of osteoblastic differentiation in new cell lines derived from spontaneous murine osteosarcomas. 815 8

Osteonectin (OTN) has been implicated in controlling cell adhesivity onto substratum and extracellular matrix (ECM) remodeling. Significant amounts of OTN were synthesized not only by normal fibroblasts and endothelial cells, but also by HT-1080 fibrosarcoma and MG-63 osteosarcoma cells. Levels of secreted OTN were likely to be slightly elevated by the addition of exogenous placental laminin (LN), but not by supplementation of plasma fibronectin (FN). Exogenously supplemented purified bone OTN was not apparently incorporated into the ECM of the adhering cells and had no effect on cell spreading and growth, whereas secretion of type I collagen or FN in the tumor cells was moderately diminished in the presence of soluble OTN. Concentration-dependent down-regulation of cellular LN secretion appeared to be most significant, suggesting that OTN participates in regulating extracellular secretion of ECM components in the cells either with or without the ability to synthesize cellular OTN.
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PMID:Osteonectin/SPARC regulates cellular secretion rates of fibronectin and laminin extracellular matrix proteins. 816 15


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