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)

It is well known that interferons inhibit cell growth. However, we found that human interferon-gamma (HuIFN-gamma) enhanced the growth of human osteosarcoma cells, HOS-Y1 cells, in a dose-dependent manner. This enhancing effect was found only under the following conditions: when the cells were precultured for 2 or 3 days and then treated with HuIFN-gamma for 2, 3, or 4 days, and when the cells were seeded at a density of 1,000 or 2,000 cells/well. The degree of enhancement of cell growth was maximum when the cells were precultured at a density of 1,000 cells/well for 3 days and then treated with HuIFN-gamma for 2 days. The enhancing effect of HuIFN-gamma disappeared in the presence of anti-HuIFN-gamma antibody. In addition, it was found that the conditioned medium from HOS-Y1 cells enhanced the growth of HOS-Y1 cells, and that the conditioned medium from HOS-Y1 cells cultured with HuIFN-gamma enhanced the cell growth more than that from cells cultured without HuIFN-gamma. Epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta 1(TGF-beta 1) did not enhance the growth of HOS-Y1 cells. These results suggest that HuIFN-gamma enhanced the cell growth by augmenting the production of unknown growth factor(s) in HOS-Y1 cells via an autocrine mechanism.
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PMID:Enhancement of the growth of human osteosarcoma cells by human interferon-gamma. 147 55

The regulation of collagenase gene expression in the human osteosarcoma-derived osteoblastic cell lines MG-63, U2-OS and human fibroblast cell line IMR-90 was investigated by Northern blot analysis. Exposure of quiescent MG-63, U2-OS and IMR-90 cells to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 10% fetal calf serum (FCS) resulted in the induction of mRNA encoding collagenase. Epidermal growth factor (EGF) induced collagenase mRNA in the IMR-90 cell but not in the MG-63 and U2-OS cells. In the IMR-90 and MG-63 cells, EGF stimulated the transcription of the c-fos and c-jun genes encoding the transcriptional factors which interact directly with the promoter region of the human collagenase gene. Parathyroid hormone and 1,25-dihydroxy-vitamin D3 did not increase the collagenase mRNA level in both osteosarcoma cells. Recombinant interleukin-1 beta (rIL-1 beta) induced collagenase and c-jun but not c-fos mRNA in the MG-63 cell. The induction by rIL-1 beta was blocked by cycloheximide and dexamethasone. Transforming growth factor beta 1 blocked the FCS-induced collagenase gene expression but partially inhibited the rIL-1 beta-induced gene expression in the MG-63 cell. These results suggest that the collagenase activity is regulated not only by post-translational modification but also at the transcriptional level by the various factors in bone.
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PMID:[Regulation of collagenase gene expression in human osteosarcoma-derived osteoblastic cell lines]. 164 84

Epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and heparin-binding growth factor-1 (HBGF-1) stimulated the proliferation of a variant of the human osteosarcoma cell line, MG-63-LS (LS = low serum). Transforming growth factor beta (TGF-beta) completely inhibited cell growth in basal medium supplemented with 2% fetal calf serum (FCS), blocked PDGF- and EGF-stimulated cell proliferation, and modulated that of HBGF-1. PDGF, but not EGF or HBGF-1, activated the inositol trisphosphate/diacylglycerol (IP3/DAG) second message system in a dose-dependent manner. EGF inhibited phosphoinositol lipid turnover and HBGF-1 and TGF-beta stimulated phosphatidylinositol hydrolysis to produce inositol phosphate (IP) but not IP3. Preincubation of quiescent cells with TGF-beta for 30-40 minutes prior to the addition of PDGF resulted in an inhibition of PDGF-induced production of IP3. This suggested that TGF-beta was an indirect inhibitor and blocked PDGF-stimulated cell growth in part by interfering with the generation of the second messenger, IP3.
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PMID:TGF-beta inhibits the platelet-derived growth factor-induced formation of inositol trisphosphate in MG-63 human osteosarcoma cells. 170 69

Twenty-five cell lines derived from nine different human cancers were tested for the cytotoxic activity of suramin. Two different initial cellular concentrations were used: C1 (800-2000 cells per well) and C2 (3000-7000 cells per well). Suramin concentrations ranged from 50 to 2500 micrograms/ml. Cytotoxicity was assessed by the MTT test. Epidermal growth factor receptors (EGFR) were assayed by competition analysis and Scatchard plots. In sixteen cell lines suramin had an unexpected growth stimulation effect at low concentration (50-125 micrograms/ml). IC50 varied from 21 micrograms/ml (osteosarcoma, OS2) to 1408 micrograms/ml (melanoma, CAL 24) and, within melanoma cell lines, it varied from 120 micrograms/ml (CAL 41) to 1408 micrograms/ml (CAL 24). The individual IC50 values were positively and significantly linked with the initial cellular density. Eighteen cell lines had measurable EGFR (six with two families of sites, twelve with one): Kd varied between 0.004 nmol/l for the highest affinity site (melanoma, CAL 7) to 1.852 nmol/l for the lowest affinity site (lung, CAL 12). There was no relation between presence or absence of EGF binding sites and distribution of IC50, but for cells with measurable EGFR there was a weak but significant correlation between the number of EGF binding sites per cell and the corresponding IC50 (r = -0.53, P = 0.021).
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PMID:Epidermal growth factor receptor expression and suramin cytotoxicity in vitro. 214 26

Epidermal growth factor (EGF) induces a rapid increase in the phosphorylation of extracellular signal-regulated kinases (ERKs) in the human osteosarcoma osteoblastic cell line G292 and in primary cultures of rat osteoblastic cells. This phosphorylation is transient and time-dependent. Maximal stimulation is attained within 1 min in G292 and within 5 min in rat osteoblastic cells. Enzymatic activity in G292 cells is also induced rapidly after EGF stimulation. Western blot analysis revealed that enhancement of the phosphorylation of ERKs in the EGF-stimulated cells is not due to an increase in ERK protein, since EGF-treatment does not lead to an increase in the absolute amount of ERKs present even after 2 days of stimulation. The pattern of expression of the ERKs observed in the two cell types differs in the apparent molecular weights observed. The most slowly migrating immunoreactive protein (approximately 45 kDa) in normal rat osteoblastic cells is ERK1, identified by an ERK1-selective antiserum. The same antiserum reacts only weakly with one of the ERK proteins (44 kDa) blotted from the human osteosarcoma cell line G292. Phorbol 12-myristate 13-acetate (PMA) is also capable of inducing ERK phosphorylation, albeit to a lasser degree. The combination of PMA and EGF does not produce a greater response than EGF alone. The role of protein kinase C (PKC) in the EGF-stimulated ERK signaling pathway was further examined by inhibition of PKC with the staurosporine analog, CGP41251, and by down-regulation of PKC via chronic treatment with PMA. Chronic PMA treatment results in a partial inhibition of the EGF-mediated phosphorylation. CGP41251 completely abolishes the increased ERK activity produced by PMA, but the effect of EGF in this regard is potentiated. We conclude that PKC and EGF act through parallel pathways to stimulate ERK phosphorylation and activity. The inhibitor studies, in addition, indicate that activation of PKC may moderate the actions of the EGF pathway via a tonic inhibitory feedback.
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PMID:EGF-mediated phosphorylation of extracellular signal-regulated kinases in osteoblastic cells. 786 Jun 43

Epidermal growth factor-like domain 7 gene (EGFL7) encodes an angiogenesis related factor and plays a crucial role in many human cancers. Previous studies have suggestedthat EGFL7 acts as a facilitator for tumor angiogenesis. However, little is known as to its role in osteosarcoma. Our aim was to investigate the expression of EGFL7 and to explore its correlation with the clinicopathological features of osteosarcoma. Tumor tissues from 32 Chinese young patients (below age of 24) with osteosarcoma were collected and subjected to EGFL7 detection by immunohistochemistry. The tissues from 10 patients with osteochondroma were collected and analyzed as controls. The intratumoral microvessel density (MVD) was examined by immunohistochemical staining using CD34 antibody. The results showed that patients with osteosarcoma had higher levels of EGFL7 in the tumor tissues compared to patients with osteochondroma (p<0.001). The expression of EGFL7 was significantly higher in advanced osteosarcoma (Enneking IIB-III) than that in early tumor stage (Enneking IA-IIA) (p<0.01). There is also a significant correlation between increased expression of EGFL7 and the Enneking stage (R = 0.714, p<0.001). Moreover, we detected a higher level of EGFL7 expression in tumor tissues of patients with recurrent or metastatic (bone or lung) osteosarcoma than those without recurrence or metastasis after 3 years' follow-up (p<0.01). There is no detectable difference of EGFL7 expression between tumor tissues from different tumor location and sex. Finally, we showed that high level of EGFL7expression was significantly correlated with high MVD (R = 0.829, p<0.001). In conclusion, our study demonstrates for the first time that there was a tumor grade-dependent up-regulation of EGFL7 in osteosarcoma. Elevated EGFL7 expression correlated with poor clinical outcome: i.e. advanced tumor stage, recurrent and metastatic osteosarcoma. Our findings support EGFL7 as a potential prognostic marker, and may provide novel insights for the diagnostics and therapeutics of osteosarcoma.
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PMID:Expression of epidermal growth factor-like domain 7 correlates with clinicopathological features of osteosarcoma. 2632 8

Epidermal growth factor-like domain-containing protein 7 (EGFL7), a member of the epidermal growth factor (EGF)-like protein family, is a potent angiogenic factor expressed in many different cell types. EGFL7 plays a vital role in controlling vascular angiogenesis during embryogenesis, organogenesis, and maintaining skeletal homeostasis. It regulates cellular functions by mediating the main signaling pathways (Notch, integrin) and EGF receptor cascades. Accumulating evidence suggests that Egfl7 plays a crucial role in cancer biology by modulating tumor angiogenesis, metastasis, and invasion. Dysregulation of Egfl7 has been frequently found in several types of cancers, such as malignant glioma, colorectal carcinoma, oral and oesophageal cancers, gastric cancer, hepatocellular carcinoma, pancreatic cancer, breast cancer, lung cancer, osteosarcoma, and acute myeloid leukemia. In addition, altered expression of miR-126, a microRNA associated with Egfl7, was found to play an important role in oncogenesis. More recently, our study has shown that EGFL7 is expressed in both the osteoclast and osteoblast lineages and promotes endothelial cell activities via extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), and integrin signaling cascades, indicative of its angiogenic regulation in the bone microenvironment. Thus, understanding the role of EGFL7 may provide novel insights into the development of improved diagnostics and therapeutic treatment for cancers and skeletal pathological disorders, such as ischemic osteonecrosis and bone fracture healing.
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PMID:EGFL7: Master regulator of cancer pathogenesis, angiogenesis and an emerging mediator of bone homeostasis. 2992

Epidermal growth factor-like domain 7 (EGFL7) is a protein specifically secreted by blood vessel endothelial cells, which plays an important role in angiogenesis. Considering the aberrant secretion of EGFL7 in osteosarcoma (OS) has not yet been elucidated, this study investigated the secretion of EGFL7 in OS and the changes in its secretion after chemotherapy. We observed increased varying secretion of EGFL7 in OS tissues compared with chondrosarcoma (CS) tissues. OS cell lines and HUVECs showed higher EGFL7 mRNA and protein expression than SW1353, with OS cells expressing the highest levels. In patient samples, EGFL7 was highly expressed in the cytoplasm of OS tumor cells and vascular endothelium cells. This overexpression was abolished in OS cell and tumor tissues when treated with chemotherapy. This study is a pioneering study to investigate EGFL7 expression and localization in human OS tissues and cell. Overexpression of EGFL-7 in response to chemotherapy suggests that it can be used as a therapeutic target for OS.
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PMID:Novel Expression of EGFL7 in Osteosarcoma and Sensitivity to Cisplatin. 3211 31