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)

Osteosarcoma is a malignant tumor of bone characterized by its high metastatic potential. For the development of metastasis, activation of matrix metalloproteinases (MMPs) is required. A novel MMPs inhibitor, reversion inducing cysteine rich protein with Kazal motifs (RECK), is known to down-regulate MMPs and suppress the invasive and metastatic potential in many tumor-derived cell lines and some types of tumors. The expression of RECK and its role in tumor invasiveness have never been studied in osteosarcoma. We examined RECK mRNA expression and MMPs activation in osteosarcoma using quantitative real time PCR, gelatin zymography, invasion assay, and transfection experiments. RECK was expressed but down-regulated in osteosarcoma cells. Activation of pro-MMP-2 was observed in all samples, whereas activation of MMP-2 and pro-MMP-9 was detected in only 11% and 7% of the samples, respectively. MMP-9 was not activated in any of the samples. The level of RECK expression was inversely correlated with pro-MMP-2 activation, and overexpression of RECK by transfection resulted in decreased pro-MMP-2 activation and reduced tumor invasiveness. These findings suggest that RECK plays an important role in the invasiveness of osteosarcoma.
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PMID:RECK expression in osteosarcoma: correlation with matrix metalloproteinases activation and tumor invasiveness. 1726 20

Osteosarcoma is the most common primary bone tumor, but the pathogenesis is not well understood. While cyclooxygeanse-2 (COX-2) is known to be closely associated with tumor growth and metastasis in several kinds of human tumors, the function of COX-2 in osteosarcoma is unclear. Therefore, to investigate the function of COX-2 in osteosarcoma, we established stable cell lines overexpressing COX-2 in U2OS human osteosarcoma cells. COX-2 overexpression as well as prostaglandin E2 treatment promoted proliferation of U2OS cells. In addition, COX-2 overexpression enhanced mobility and invasiveness of U2OS cells, which was accompanied by increases of matrix metalloproteinase-2 and -9 (MMP-2 and -9) activities. Selective COX-2 inhibitors, NS-398 and celecoxib, inhibited cell proliferation and abrogated the enhanced mobility, invasiveness and MMP activities induced by COX-2 overexpression. These results suggest that COX-2 is directly associated with cell proliferation, migration and invasion in human osteosarcoma cells, and the therapeutic value of COX-2 inhibitors should be evaluated continuously.
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PMID:Cyclooxygenase-2 promotes cell proliferation, migration and invasion in U2OS human osteosarcoma cells. 1793 34

Cancer cells, characterized by local invasion and distant metastasis, are very much dependent on the extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. In this study, we reported the effects of disulfiram, a clinically used anti-alcoholism drug, on tumor invasion suppression, as well as its effects on the activity of MMP-2 and MMP-9 in human osteosarcoma cells (U2OS). Disulfiram has been used for alcohol aversion therapy. However, recent reports have shown that disulfiram may have potential in the treatment of human cancers. Herewith, we showed that the anti-tumor effects of disulfiram, in an invasion assay using U2OS cells and that disulfiram has a type IV collagenase inhibitory activity that inhibits expression of genes and proteins responsible for both cell and non-cell mediated invasion on pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9 and it regulated the invasion of human osteosarcoma cells. These observations raise the possibility of disulfiram being used clinical for the inhibition of cancer invasion.
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PMID:Disulfiram suppresses invasive ability of osteosarcoma cells via the inhibition of MMP-2 and MMP-9 expression. 1804 5

The Forkhead box M1 (FoxM1) protein is a proliferation-specific transcription factor that plays a key role in controlling both the G(1)/S and G(2)/M transitions through the cell cycle and is essential for the development of various cancers. We show here that FoxM1 directly activates the transcription of the c-Jun N-terminal kinase (JNK1) gene in U2OS osteosarcoma cells. Expression of JNK1, which regulates the expression of genes important for the G(1)/S transition, rescues the G(1)/S but not the G(2)/M cell cycle block in FoxM1-deficient cells. Knockdown of either FoxM1 or JNK1 inhibits tumor cell migration, invasion, and anchorage-independent growth. However, expression of JNK1 in FoxM1-depleted cells does not rescue these defects, indicating that JNK1 is a necessary but insufficient downstream mediator of FoxM1 in these processes. Consistent with this interpretation, FoxM1 regulates the expression of the matrix metalloproteinases MMP-2 and MMP-9, which play a role in tumor cell invasion, through JNK1-independent and -dependent mechanisms in U2OS cells, respectively. Taken together, these findings identify JNK1 as a critical transcriptional target of FoxM1 that contributes to FoxM1-regulated cell cycle progression, tumor cell migration, invasiveness, and anchorage-independent growth.
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PMID:FoxM1 regulates transcription of JNK1 to promote the G1/S transition and tumor cell invasiveness. 1852 73

Proteomics is a novel molecular profiling technology. It is mainly concerned with determining the structure, expression, localization, biochemical activity, interactions, and cellular roles of any proteins. Clinical research hopes to benefit from proteomics in the identification of new drug targets and the development of new diagnostic markers. Better to understand the mechanisms by which ascofuranone (AF), an isoprenoid antibiotic, regulates physiological or pathological events and induces responses in the pharmacological treatment of cancer, we performed differential analysis of the human osteosarcoma cells U2OS proteomes in response to this agent. The U2OS cell proteomes with and without treatment with AF were compared using two-dimensional electrophoresis, matrix-assisted laser desorption/ionization mass spectrometry, and bioinformatics. The largest differences in protein expression were observed for hydroxyindole O-methyltransferase, syntaxin-binding protein 1, the matrix metalloproteinase (MMP)-2, urokinase receptor, and endothelial protein C receptor. Changes in expression and activity of some selected proteins were confirmed by Western blotting, zymography, and reverse transcription-polymerase chain reaction analysis. In particular, we observed downregulated tumor growth related-proteins such as MMP-2 and endothelial protein C receptor. According to these results, AF might be useful as a potent chemotherapeutic agent.
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PMID:Proteome profiling of U2OS cell line in response to a prenylphenol antibiotic isolated from a phytopathogenic fungus. 1875 62

Osteosarcoma is the most common primary malignancy of bone in children and young adults. There is a paucity of tumorigenic and highly metastatic human osteosarcoma cell lines that have not been further transformed by exogenous means. Here we establish and characterize a highly metastatic human osteosarcoma cell line that is derived from a poorly metastatic MG63 line through serial passage in nude mice via intratibial injections. The occasional pulmonary metastases developed from MG63 were harvested and repassaged in mice until a highly metastatic subline (MG63.2) was established. The parental MG63 and highly metastatic MG63.2 cells were further characterized in vitro and in vivo. MG63.2 cells demonstrated increased cell migration and invasion compared to the parental MG63 cells. Conversely, cell adhesion was significantly greater in MG63 cells when compared to the MG63.2 cells. MG63.2 cells grew at a slightly slower rate than that of the parental cells. When injected into nude mice, MG63.2 cells had a greater than 200-fold increase in developing pulmonary metastases compared to the parental MG63 cells. MG63.2 cells also formed larger primary tumors when compared to the parental MG63 cells. Further analysis revealed that ezrin expression was up-regulated in the metastatic MG63.2 cells. Interestingly, expressions of MMP-2 and MMP-9 were down-regulated, and expression of TIMP-2 was up-regulated in the MG63.2 cells. Taken together, we have established and characterized a highly metastatic human osteosarcoma cell line that should serve as a valuable tool for future investigations on the pathogenesis, metastasis, and potential treatments of human osteosarcoma.
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PMID:Establishment and characterization of a new highly metastatic human osteosarcoma cell line. 1936 54

This work investigates the effect of cell-collagen I interactions on the synthesis and activation of MMP-2, as well as synthesis of MT1-MMP and TIMP-1, by using an in vitro model with 3D fibrillar and 2D monomeric collagen. In order to reveal whether the metastasis-associated protein S100A4 can influence the cell's response to the two forms of collagen, osteosarcoma cell lines with high and low endogenous levels of S100A4 were used. Attachment of osteosarcoma cells to 3D fibrillar and 2D monomeric collagen resulted in opposite effects on MMP-2 activation. Attachment to 3D fibrillar collagen decreased activation of proMMP-2, with a corresponding reduction in MT1-MMP. By contrast, attachment to monomeric collagen increased the amount of fully active MMP-2. This was caused by a reduction in TIMP-1 levels when cells were attached to monomeric 2D collagen. The effect of collagen on proMMP-2 activation was independent of endogenous S100A4 levels, whereas synthesis of TIMP-1 was dependent on S100A4. When cells were attached to monomeric collagen, cells with a high level of S100A4 showed a greater reduction in the synthesis of TIMP-1 than did those with a low level of S100A4. Taken together, this study shows that synthesis and activation of MMP-2 is affected by interactions between osteosarcoma cells and collagen I in both fibrillar and monomeric form.
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PMID:Collagen I regulates matrix metalloproteinase-2 activation in osteosarcoma cells independent of S100A4. 1968 73

Osteosarcoma, the most common primary bone tumor in young adults, is characterized by local invasion and distant metastasis. But detailed mechanisms of tumorigenicity and metastasis of osteosarcoma are not well known. We report the involvement of calpains, a family of calcium-activated, cysteine proteases, in the invasive and metastatic processes of human osteosarcoma cells. By using siRNA treatment, the expression of mu- and m-calpains were downregulated in human Saos-2 osteosarcoma cells. Both the adhesive and invasive potentials were significantly attenuated in calpain siRNA-transfected human Saos-2 osteosarcoma cells. MMPs are the main factors involved in malignant tumor invasion and metastasis. siRNA of calpains also significantly inhibited the secretion of MMP-2 in Saos-2 cells. These results suggest that mu- and m-calpains are important in the invasion and metastasis of human osteosarcoma cells, and calpains might be targeted to reduce tumor progression.
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PMID:Silencing of calpain expression reduces the metastatic potential of human osteosarcoma cells. 1974 55

The mouse polyoma virus induces a broad array of solid tumors in mice of many inbred strains. In most strains tumors grow rapidly but fail to metastasize. An exception has been found in the Czech-II/Ei mouse in which bone tumors metastasize regularly to the lung. These tumors resemble human osteosarcoma in their propensity for pulmonary metastasis. Cell lines established from these metastatic tumors have been compared with ones from non-metastatic osteosarcomas arising in C3H/BiDa mice. Osteopontin, a chemokine implicated in migration and metastasis, is known to be transcriptionally induced by the viral middle T antigen. Czech-II/Ei and C3H/BiDa tumor cells expressed middle T and secreted osteopontin at comparable levels as the major chemoattractant. The tumor cell lines migrated equally well in response to recombinant osteopontin as the sole attractant. An important difference emerged in assays for invasion in which tumor cells from Czech-II/Ei mice were able to invade across an extracellular matrix barrier while those from C3H/BiDa mice were unable to invade. Invasive behavior was linked to elevated levels of the metalloproteinase MMP-2 and of the transcription factor NFAT. Inhibition of either MMP-2 or NFAT inhibited invasion by Czech-II/Ei osteosarcoma cells. The metastatic phenotype is dominant in F1 mice. Osteosarcoma cell lines from F1 mice expressed intermediate levels of MMP-2 and NFAT and were invasive. Osteosarcomas in Czech-II/Ei mice retain functional p53. This virus-host model of metastasis differs from engineered models targeting p53 or pRb and provides a system for investigating the genetic and molecular basis of bone tumor metastasis in the absence of p53 loss.
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PMID:Polyoma virus-induced osteosarcomas in inbred strains of mice: host determinants of metastasis. 2010 4

Osteosarcoma (OS) is among most common malignant tumour of bone. Matrix metalloproteinases (MMPs) are predominantly associated with poor prognosis of several cancers, although some of them, like MMP-8, seem to have a protective role in some cancers. We analyzed the distribution patterns of MMP-2, -8, -13, -26, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in 25 OS patients. MMP-2, -8, -13, -26 and TIMP-1 were mostly detected in sarcoma cells. Response to chemotherapy affected the amount of MMP-2, -8, and -13 in resection sections when compared to biopsies: patients with excellent or good response had less positivity to MMP-2 in chemotherapy samples than those with moderate or poor response. We conclude that MMP-2, -8, -13, -26, and TIMP-1 are expressed in OS tissue, and all, except protective MMP-8, were also found in metastases indicating that MMPs and TIMP-1 can participate in the OS progression.
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PMID:Expression of matrix metalloproteinases-2, -8, -13, -26, and tissue inhibitors of metalloproteinase-1 in human osteosarcoma. 2088 Jul


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