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)

Several studies overwhelmingly support the notion that decorin (DCN) is involved in matrix assembly, and in the control of cell adhesion and proliferation. However, nothing is known about the role of DCN during cell migration. Cell migration is a tightly regulated process which requires both adhesion (at the leading edge of the cell) and de-adhesion (at the trailing edge of the cell) from the substratum. We have determined in this study the effect of DCN on MG-63 osteosarcoma cell migration and have analyzed whether its effect is mediated by the protein core and/or the glycosaminoglycan side chain. DCN impeded the migration-promoting effect of matrix molecules (fibronectin, collagen type I) known to interact with the proteoglycan. Conversely, DCN did not counteract the migration-promoting effect of fibrinogen lacking proteoglycan affinity. DCN bearing dermatan-sulfate chains (i.e., skin and cartilage DCN) was about 20-fold more effective in inhibiting cell migration than DCN bearing chondroitin-sulfate chains (i.e., bone DCN). In addition, chondroitinase AC-treatment of cartilage DCN (which specifically removes chondroitin-sulfate chains) did not attenuate the inhibitory effect of this proteoglycan, while cartilage DCN deprived of both chondroitin- and dermatan-sulfate chains failed to alter cell migration promoted by either fibronectin or its heparin- and cell-binding domains. These data assert that the dermatan-sulfate chains of DCN are responsible for a negative influence on cell migration. However, isolated glycosaminoglycans failed to alter cell migration promoted by fibronectin, indicating that strongly negatively charged glycosaminoglycans alone cannot account for the impaired cell motility seen with DCN. Overall, these results show that the inhibitory action of DCN is dependent of substratum binding, is differentially mediated by its glycosaminoglycan side chains (chondroitin-sulfate vs. dermatan-sulfate chains), and is independent of a steric hindrance effect exerted by its glycosaminoglycan side chains.
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PMID:Decorin inhibits cell migration through a process requiring its glycosaminoglycan side chain. 1053 75

Cell culture in collagen lattice is known to be a more physiological model than monolayer for studying the regulation of extracellular matrix protein deposition. The synthesis of sulfated glycosaminoglycans (GAG) and dermatan sulfate (DS) proteoglycans by 3 cell strains were studied in confluent monolayers grown on plastic surface, in comparison to fully retracted collagen lattices. Cells were labelled with 35S-sulfate, followed by GAG and proteoglycan analysis by cellulose acetate and SDS-polyacrylamide gel electrophoresis, respectively. The 3 cell strains contracted the lattice in a similar way. In monolayer cultures, the major part of GAG was secreted into culture medium whereas in lattice cultures of dermal fibroblasts and osteosarcoma MG-63 cells but not fibrosarcoma HT-1080 cells, a higher proportion of GAGs, including dermatan sulfate, was retained within the lattices. Small DS proteoglycans, decorin and biglycan, were detected in fibroblasts and MG-63 cultures. They were preferentially trapped within the collagen gel. In retracted lattices, decorin had a higher Mr than in monolayer. Biglycan was detected in monolayer and lattice cultures of MG-63 cells but in lattice cultures only in the case of fibroblasts. In this last case, an up regulation of biglycan mRNA steady state level and down regulation of decorin mRNA was observed, in comparison to monolayers, indicating that collagen can modulate the phenotypical expression of small proteoglycan genes.
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PMID:Modulation of sulfated glycosaminoglycan and small proteoglycan synthesis by the extracellular matrix. 1082 30

Osteosarcoma cells are useful for investigating bone metabolism as malignant counterpart of osteoblasts. In hematogenous metastases of osteosarcoma cells, the cells need to adjust to various changes in pericellular environment. The changes in pericellular environment may change intracellular environment and consequently the secretion of matrix metalloproteinases (MMPs) which destroy extracellular matrices. In this report, a new cell line, KOS-1, derived from human osteoblastic osteosarcoma was established, and we assumed various culture conditions containing ingredients of the extracellular matrix to make a comparative study on MMPs detected from the culture supernatants. A wide spectrum of MMPs, including MMP-1 and -3 which were increased in the presence of interleukin 1 beta, was detected in this cell line. Production of MMP-1, the enzyme which decomposes types I, II, III and X collagen, by the cells, was increased in the presence of type I collagen. MMP-3 (stromelysin-1) which degrades types III and IV collagen, laminin, fibronectin, proteoglycan, etc. was produced more abundantly in the presence of type IV collagen. MMP-2 (72-kd type IV collagenase/gelatinase A) activity was found to be increased in the presence of gelatin and type IV collagen. The MMPs production in cultured osteosarcoma cells was changed depending on the culture conditions. This indicates that the same osteosarocma cells produce different amounts and kinds of enzymes involved in local infiltration and remote metastases and increase the production of the enzymes most required under a specific environment.
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PMID:Establishment of an osteoblastic osteosarcoma cell line and effects of cell culture conditions on secretion of matrix metalloproteinases from the cultured osteosarcoma cells. 1094 49

Complex formation of transforming growth factor-beta (TGF-beta) with the small proteoglycan decorin has been considered to inactivate the cytokine. However, neither the TGF-beta-mediated stimulation of the retraction of collagen lattices in culture nor the enhanced transcription of biglycan were influenced by an excess of native decorin in the culture medium. In contrast, when MG-63 osteosarcoma cells were transfected with sense- or antisense-decorin-cDNA, which led to an over- or under-expression of the proteoglycan, they responded to TGF-beta differently. An inverse correlation between decorin expression and the TGF-beta-mediated stimulation of collagen gel retraction and biglycan induction, respectively, was found. These results are best explained by assuming that decorin is not inactivating but sequestering TGF-beta in the extracellular matrix.
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PMID:Influence of decorin expression on transforming growth factor-beta-mediated collagen gel retraction and biglycan induction. 1110 52

The purpose of this study was to examine if an unusual bilaminar pattern of lateral tibial condyle cartilage layer on the fat-suppressed three-dimensional (3D) spoiled gradient echo sequence is artifactual or correlates with structural and/or biochemical composition of cartilage. The laminar appearance of the lateral tibial condyle cartilage layer was studied on fat-suppressed 3D spoiled gradient echo MR images of the knee joint in 67 patients (mean age: 28y) performed at 1.0 Tesla. After i.v. administration of gadopentetate dimeglumine, diffusion of the contrast media into cartilage layer was qualitatively analysed over time on inversion recovery spin echo images of knee joints of five asymptomatic volunteers (mean age: 25y). In a patient with osteosarcoma and total knee replacement, MR examination of cartilage layer of lateral tibial plateau was compared with histologic specimens stained with Safranin-O, demonstrating proteoglycan distribution in cartilage. The retrospective analysis of 67 knee joints revealed a bilaminar appearance of lateral tibial condyle cartilage layer in the gradient echo images in the majority of cases (81%) with a statistically significant tendency to a trilaminar pattern in patients older than 20 years. With i.v. contrast administration, the contrast enhancement was only observed in the superficial zone of tibial cartilage layer. Histologic specimens in one patient demonstrated a good correlation between thickness of proteoglycan-free and proteoglycan-rich laminae of lateral tibial condyle on Safranin-O staining with hyperintense and hypointense zones, respectively, on corresponding fat-suppressed 3D spoiled gradient echo images (correlation coefficient of 0.87). Bilaminar pattern of tibial condyle cartilage layer on fat-suppressed 3D spoiled gradient echo images in younger subjects is not an artifact or an intrachondral lesion, but it may represent a regional difference in composition of extracellular cartilage matrix possibly produced by a highly-oriented collagen fiber structure associated with a high concentration of proteoglycans in the middle and deep portion of the cartilage layer.
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PMID:Bilaminar pattern of tibial condyle cartilage layer on the fat-suppressed 3D gradient echo images: artifact or structural and biochemical difference in composition of cartilage? 1135 56

Clinical and in vitro studies have demonstrated that fluoroquinolones are toxic to chondrocytes; however, the exact mechanism of fluoroquinolone arthropathy is unknown. We investigated the toxicity of ciprofloxacin on normal cartilage and on cartilaginous tumors. Normal human cartilage, enchondroma, and chondrosarcoma explants were cultured either alone or with the addition of ciprofloxacin at 1, 10, or 20 mg/L of medium. Samples were collected up to twenty-one days after treatment and were processed for electron microscopy and conventional light microscopy. The specimens were characterized morphologically with use of conventional light microscopy, electron microscopy, and immunohistochemistry to identify extracellular matrix, cell proliferation, and apoptosis. Cultures of normal chondrocytes expressed type-II collagen. Electron microscopy revealed a large amount of glycogen in the cells; the presence of fat droplets, rough endoplasmic reticulum, and prominent Golgi apparatus; and a proteoglycan layer surrounding the cells. With prolonged ciprofloxacin treatment and with increased doses, there was an increase in dilated rough endoplasmic reticulum, the appearance of phagosomes, and disintegrated bundles of vimentin filaments. The treated chondrocytes showed a decrease in cell proliferation, but there was no induction of apoptosis or effect on the expression of extracellular matrix proteins. Ciprofloxacin-treated chondrosarcoma cultures and tissue samples showed changes in cartilage matrix composition. Ultrastructural analysis demonstrated clumped glycogen, dilation of endoplasmic reticulum, numerous abnormal lysosomes containing degeneration products, and a decreased proteoglycan deposit surrounding the tumor cells. Treated chondrosarcoma cells and tissue specimens did not proliferate, and apoptosis was induced. In contrast, the in vitro growth of other noncartilaginous malignant tumors like osteosarcoma and liposarcoma was unaffected by ciprofloxacin. Our results indicate that ciprofloxacin is toxic to chondrocytes. In vitro and in vivo treated chondrosarcomas are the most affected.
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PMID:Fluoroquinolone's effect on growth of human chondrocytes and chondrosarcomas. In vitro and in vivo correlation. 1168 46

We investigated the differentiation potential into various mesenchymal cell lineages of the clonal cell line (USAC) that was isolated from a human chondrogenic osteosarcoma. USAC cells produced types II and X collagens and proteoglycan, indicating chondrocyte differentiation. Production of type I collagen and osteocalcin by USAC cells demonstrated osteoblastic properties. They also differentiated into adipocytes generating numerous lipid droplets in their cytoplasm. Recombinant human bone morphogenetic protein-2 (rhBMP-2) increased production of proteoglycan, types II and X collagens and osteocalcin. This indicates that rhBMP-2 promotes both chondroblastic and osteoblastic differentiation in USAC cells. rhBMP-2 inhibited adipocyte differentiation. USAC cells transplanted with rhBMP-2 into the peritoneal cavities of athymic mice using diffusion chambers generated cartilage and bone more effectively in the diffusion chambers than those produced without rhBMP-2. Although USAC cells also produced adipose tissue in the diffusion chambers following transplantation with or without rhBMP-2, rhBMP-2 treatment reduced the amounts of adipose tissue. These results demonstrate that USAC is a suitable model to explore regulatory mechanisms involved in human mesenchymal cell differentiation.
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PMID:A human chondrogenic cell line retains multi-potency that differentiates into osteoblasts and adipocytes. 1505 Aug 95

The third alpha-chain of type V collagen, alpha3(V) chain, was initially identified in the placenta more than 20 years ago, but was poorly characterized with regard to its expression and function. We generated a specific monoclonal antibody against the N-terminal domain of the pro-alpha3(V) chain and examined gene expression using immunohistochemical methods combined with in situ hybridization. The pro-alpha3(V) chain was seen in funis and amnion, but not chorionic villi and deciduas of mouse placenta. In mouse embryo, the transcripts of the pro-alpha3(V) gene were seen in tissues that were related to bone formation as well as developing muscle and nascent ligament previously reported. However, immunohistochemistry showed that pro-alpha3(V) protein accumulated rather in the developing bone of mouse embryo. On the other hand, the N-terminal globular domain of the pro-alpha3(V) chain has a unique structure that contains a highly basic segment of 23 amino acids. The peptide derived from the basic segment showed a specific adhesive feature to osteosarcoma cells but not to chondrosarcoma cells. The four heparin binding sites in the basic segment equally contribute toward adhesion to the osteosarcoma cells. Our data suggested that N-terminal globular domain of the pro-alpha3(V) chain influence bone formation of osteoblasts through proteoglycan on the cell surface during development or regeneration.
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PMID:Pro-alpha3(V) collagen chain is expressed in bone and its basic N-terminal peptide adheres to osteosarcoma cells. 1590 93

The human osteosarcoma cell line Saos-2 is widely used as a model system for human osteoblastic cells, though its phenotypic stability has not been ascertained. We therefore propagated these cells over 100 passages and compared relevant phenotypic properties. In general, higher passage cells exhibited higher proliferation rates and lower specific alkaline phosphatase activities, though mineralization was significantly more pronounced in cultures of late passage cells. Whereas expression of most genes investigated did not vary profoundly, some genes exhibited remarkable differences. Decorin, for instance, that has been discussed as a regulator of proliferation and mineralization, is strongly expressed only in early passage cells, and two receptors for pleiotrophin and midkine exhibited an almost mutually exclusive expression pattern in early and late passage cells, respectively. Our observations indicate that special care is required when results obtained with Saos-2 cells with different culture history are to be compared.
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PMID:Phenotypic instability of Saos-2 cells in long-term culture. 1593 97

Versican, a large sized chondroitin-sulphate proteoglycan (PG), and its binding partner, hyaluronan (HA), are extracellular matrix (ECM) components that play an essential role in transformed cell behavior. Expression of certain versican isoforms has been implicated in cell migration and proliferation of cancer cells and, on the other hand, disruption of HA synthesis by inhibiting hyaluronan synthase-2 (HAS2) expression in osteosarcoma cells by suppressing cell proliferation, invasiveness and motility. Considering that growth factors, such as TGF-beta, bFGF and PDGF-BB, are important regulators for the expression of the ECM macromolecules, in this study we examined the effect of these growth factors on the expression of the various versican isoforms, HA synthases as well as HA synthesis by MG-63 osteosarcoma cells and normal human osteoblastic periodontal ligament cells (hPDL). Real-time PCR and metabolic labelling followed by fine HPLC analysis coupled to radiochemical detection were the methods utilized. It was found that, contrary to normal hPDL cells, osteosarcoma MG-63 cells do not constitutively express the versican isoforms V0 and V1. Exogenous addition of TGF-beta2 stimulated the versican transcript levels mainly by forcing osteosarcoma cells to express V1 and V0 isoforms. PDGF-BB and bFGF had only minor effects in these cells. In hPDL cells a strong stimulation of the V3 transcript by all growth factors was observed. TGF-beta2 was also the major stimulator of HAS2 isoform expression as well as hyaluronan synthesis in osteosarcoma cells, while PDGF-BB exerted dominant influence on HAS2 isoform expression and hyaluronan biosynthesis by osteoblasts. The obtained results show for the first time that TGF-beta2 triggers the malignant phenotype pattern of versican and hyaluronan expression in human osteosarcoma cells and indicate that this growth factor may account for the metastatic potential of these cells.
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PMID:Transforming growth factor-beta as a key molecule triggering the expression of versican isoforms v0 and v1, hyaluronan synthase-2 and synthesis of hyaluronan in malignant osteosarcoma cells. 1654 Apr 32


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