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)

Cultures of normal diploid fibroblasts and of a human osteosarcoma cell line (MG-63) are shown to be able to produce a factor which promotes the growth of B cell hybridomas (hybridoma growth factor, HGF). The induction is stimulated by treatment of the cells with interleukin 1 (IL 1) (alpha or beta) or polyriboinosinic-polyribocytidylic acid [poly(rI).poly(rC)]. Combined treatment with cycloheximide and actinomycin D also stimulates production and enhances production induced by IL 1 or poly(rI).poly(rC). Extremely small doses of IL 1 (0.1 units/ml) are active as inducer of HGF. Also, under optimal conditions the yield of HGF can attain as much as 10(4) units/ml. Tumor necrosis factor (TNF-alpha), which otherwise shares various properties with IL 1, is a weak inducer of HGF. Although there is a superficial resemblance between induction of HGF and that of interferon-beta, the two activities are serologically distinct and conditions for their induction are quite different. In fact, conditions for induction of HGF are indistinguishable from those described for the induction of the mRNA of the so-called 26-kDa protein (also known as interferon-beta 2). Finally, the HGF derived from IL 1- or poly(rI).poly(rC)-treated fibroblasts is serologically not distinguishable from that produced by mitogen-stimulated peripheral blood leukocytes.
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PMID:Interleukin 1 and poly(rI).poly(rC) induce production of a hybridoma growth factor by human fibroblasts. 354 52

Monkey periodontal ligament fibroblasts (MPLF cells), human gingival fibroblasts (HGF cells), rat embryonic calvaria cells (REC cells), porcine periodontal ligament epithelial cells (PPLE cells) and rat osteosarcoma 17/2 cells (ROS cells) were incorporated into 3-dimensional collagen gels plated in 60 mm Petri dishes in order: first, to measure the capacity of these cell types to contract; second, to investigate cell-collagen and intercellular relationships during contraction; and third, to define the cellular contribution to tissue contraction in an in vitro system. Measurements at times up to 72 h on 3 ml gels containing 5 x 10(5) cells and with a collagen concentration of 1.20 mg/ml showed that MPLF cells contracted the gels at a significantly greater rate (P less than 0.001) than did the other cell types. In addition, contraction started sooner and was of greater extent than with the other cells. HGF cells contracted the gels more rapidly than REC and PPLE cells, while ROS cells caused no contraction. Several stages of gel compaction could be defined: (1) the attachment of cells to collagen; (2) cellular spreading within the collagen fibre matrix; (3) organization and alignment of collagen fibres by cell processes; (4) cell migration; (5) establishment of intercellular contacts; and (6) the development of a cellular reticular arrangement within the gel and the extension of this arrangement into a 3-dimensional, tissue-like, honeycomb network. Electron microscopic observations on 0.1 ml gels containing MPLF cells showed that, in the early contractile phase, numerous cell processes attached to or enclosed collagen fibrils. These processes contained microfilamentous material and few organelles. In compacted gels, the cells contained an increased amount of distended rough endoplasmic reticulum and Golgi membranes. Since MPLF cells have the capacity for vigorous contraction of the collagen gels and since they develop a reticular, 3-dimensional structure in compacted gels that is reminiscent of the relationship of periodontal ligament fibroblasts to collagen fibres in vivo, it is suggested that they could provide the major force necessary for tooth eruption in vivo. This system also provides a well-defined in vitro model to study the sequential stages that occur during contraction processes.
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PMID:Contraction and organization of collagen gels by cells cultured from periodontal ligament, gingiva and bone suggest functional differences between cell types. 679 46

Overexpression of the hepatocyte growth factor receptor (Met/HGF receptor), a transmembrane tyrosine kinase encoded by the met proto-oncogene, has been associated with tumor progression in different human carcinomas. More recently, the Met/HGF receptor has also been described in tumor cell lines of mesenchymal origin, suggesting the existence of an autocrine loop that may contribute to the pathogenesis of sarcomas. In this study, we analyzed the expression of Met/HGF receptor by Western blotting and immunohistochemistry in frozen samples of 87 primary tumors of bone and soft tissues. Among benign tumors, overexpression was consistently found only in giant-cell tumor, a locally aggressive lesion that may also, although rarely, spread to the lung. Among malignant lesions, the presence of the Met/HGF receptor was detected in a relevant percentage of primaries and in almost all of the recurrences. The highest levels of Met/HGF receptor were found in osteosarcoma, a highly aggressive tumor that typically permeates the host bone and rapidly expands to the soft tissues. On the contrary, only low levels of Met/HGF receptor were found in chondrosarcoma, a slowly growing tumor that usually expands without massive destruction of the surrounding structures. These data indicate an association of Met/HGF expression with local aggressiveness in human mesenchymal tumors. The finding of Met/HGF receptor overexpression in all of the osteosarcomas suggests a role for the met proto-oncogene in the pathogenesis of this tumor.
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PMID:Expression of Met/hepatocyte growth factor receptor gene and malignant behavior of musculoskeletal tumors. 886 70

Permanent human osteosarcoma cell lines are important tools for the study of bone cancer. As representative of an osteoblastic phenotype, they partly reflect their normal osteoblastic counterparts and, thus, may represent appropriate models to investigate the mechanisms involved in bone remodelling and in haematopoietic differentiation. In the present work, we describe a new human cell line, CAL 72, obtained from an osteosarcoma of the knee of a 10-year-old boy. These cells grow in continuous culture, and karyotypic analysis has revealed clonal abnormalities in number and structure, especially loss of chromosome Y. These cells exhibit morphological, immuno-histochemical and molecular characteristics of the osteoblastic lineage. Using RT-PCR, we have shown that the CAL 72 cell line expresses high levels of mRNA coding for several cytokines, such as G-CSF, GM-CSF, IL-1beta and IL-6. In view of this expression profile, the CAL 72 phenotype appears to be closer to normal primary osteoblasts than other reported osteosarcomas. Moreover, these cells express mRNA for both HGF and its receptor c-MET, suggesting that this autocrine loop might contribute to the invasiveness of the tumour from which CAL 72 originated.
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PMID:Establishment, characterisation and partial cytokine expression profile of a new human osteosarcoma cell line (CAL 72). 1038 64

Signal transduction downstream HGF receptor (MET) activation involves multiple pathways that account for mitogenesis, motility and morphogenesis in a cell type-dependent fashion. MET receptor is aberrantly expressed in almost 100% of human osteosarcomas. We analyzed the effect of the MET receptor activation in five human osteosarcoma cell lines evaluating the levels of HGF-dependent activation of MAPK and PKB/AKT as biochemical readouts of mitogenic and invasive responses, respectively. All the cell lines tested expressed high levels of the MET proto-oncogene. Four cell lines showed activation of the MAPK cascade upon HGF stimulation, suggesting that this growth factor serves a common proliferative function in osteosarcomas. Two lines showed activation of PKB/AKT that is known to be involved in migration mediated by HGF receptor. Accordingly, cell lines where MAPK cascade was activated responded to HGF with increased proliferation, while induction and inhibition of PKB/AKT activity corresponded to acquisition or block of the invasive-motile response to HGF, respectively. Both the HGF dependent responses were reverted by the specific MET inhibitor K252a. These data show that HGF activates both the mitogen and motogen machinery in osteosarcoma cells and suggest that HGF might promote their malignant behavior by concomitant activation of different pathways and biological functions.
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PMID:Role of the MET/HGF receptor in proliferation and invasive behavior of osteosarcoma. 1270 13

To further characterize the role of hepatocyte growth factor-scatter factor (HGF-SF) and its receptor (c-Met) in osteosarcoma (OS), human OS cell lines with low (SAOS-2) and high (SAOS-LM2) metastatic potential, and cell lines derived from spontaneous canine OS were studied. All cell lines were evaluated for c-Met and HGF-SF expression and receptor activation using Northern, RT-PCR, and Western blot analyses, respectively. Functional activity of receptor-ligand interaction was measured using c-Met phosphorylation status, proliferation assays (anchorage-dependent and -independent), Matrigel invasion, modulation of urokinase plasminogen activator (uPA) expression, and cell dispersion (scattering). All cell lines exhibited steady-state mRNA expression of c-Met. The canine OS cell lines also expressed HGF-SF mRNA as determined by RT-PCR analysis. Western analysis showed c-Met protein expression and HGF-stimulated (human) or constitutive (canine) receptor autophosphorylation. Treatment with recombinant human HGF resulted in enhanced proliferation in 3 of 5 OS cell lines and enhanced colony formation in 2 of 5 OS cell lines. Matrigel invasion was significantly enhanced in 3 of the cell lines and uPA levels were significantly increased in the SAOS-2 cells following HGF treatment. Scattering was enhanced in both the SAOS-2 and SAOS-LM2 cells. These data support the involvement of c-Met and HGF-SF in the growth and progression of human and canine OS, and may offer new targets for the development of therapeutic strategies for OS.
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PMID:c-Met tyrosine kinase receptor expression and function in human and canine osteosarcoma cells. 1452 31

Osteosarcoma is a common malignant bone tumor. Cisplatin (CDDP) achieves a high response rate in osteosarcoma. However, osteosarcoma usually exhibits cisplatin resistance. Many members of receptor tyrosine kinases (RTKs)(1) have been demonstrated to be overexpressed and constitutively activated in various tumors including osteosarcoma, resulting in malignant progression and insensitivity to chemotherapy. Hepatocyte growth factor receptor (HGFR/c-Met) also appears overexpressed and activated in osteosarcoma cells. Nevertheless, which role of c-Met activation in cisplatin efficacy against osteosarcoma cells remains still elusive. This study found that inhibition of c-Met activity by PHA-665752 or blockade of the interaction of autocrined HGF with c-Met with neutralizing anti-HGF antibody promoted cisplatin efficacy in osteosarcoma cells, while addition of recombinant human HGF (rh-HGF) counteracts cisplatin cytotoxicity. Specifically, we demonstrated that inhibition of c-Met activity led to suppression of the PI3K-Akt pathway, thus enhancing cisplatin chemosensitivity. Our study clearly suggests that inhibition of c-Met activity can effectively sensitize osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling.
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PMID:Inhibition of c-Met activation sensitizes osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling. 2282 99