Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three new cell lines of human glioblastoma have been established. These cells co-expressed hepatocyte growth factor (HGF) and its receptor, c-Met, genes in vitro. Reverse-transcriptase/polymerase-chain reaction study revealed that the cells also expressed gene for HGF activator, a recently cloned serine proteinase, suggesting that HGF might have a role in glioma cells in vitro as an autocrine factor. The activator mRNA was also detected in other well-established glioma cell lines, glioma tissues and normal brain. The concomitant expression of HGF, HGF activator and c-met was also detected in one glioblastoma case in vivo out of five tested.
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PMID:Concomitant expression of hepatocyte growth factor (HGF), HGF activator and c-met genes in human glioma cells in vitro. 755 48

Expression of c-Met, the receptor for hepatocyte growth factor (HGF), and the biological roles of HGF were examined in cultured human glioma cells. All of the 5 glioma cell lines examined expressed c-Met protein as well as the c-met gene. Expression of the c-met gene was also confirmed in a glioblastoma tissue. Three cell lines (MGM-3, U251, KG-1-C) demonstrated chemotactic response to HGF in a dose-dependent manner. The response was not only chemotactic but also chemokinetic as judged by a checkerboard analysis. The amounts of c-Met mRNA and protein were abundant in the cell lines which showed a migratory response to HGF. Moreover, c-Met protein expression was highest in U251 with the highest migratory response to HGF. Among the cell lines, KG-1-C produced notable amounts of HGF protein as well as of c-Met, suggesting that HGF may act in an autocrine fashion in this case. HGF did not act as an apparent growth factor in the glioma cell lines examined. Furthermore, HGF stimulated the production of metalloproteinase, probably gelatinase A, in U251 cells.
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PMID:Effects of hepatocyte growth factor (HGF) on human glioma cells in vitro: HGF acts as a motility factor in glioma cells. 864 32

Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a cytokine that induces cell motility in vitro and angiogenesis in vivo. SF appears to be a determinant of the malignant phenotype in certain systemic cancers. We detected SF in extracts prepared from human gliomas, with the highest levels found in malignant tumors. Human glioblastoma cells expressed both SF and its receptor (c-met protein) in vivo, as demonstrated by immunohistochemistry. Consistent with these observations, we found moderate to high levels of production of immunoreactive and biologically active SF by cultured human glioblastoma cells (3 of 8 lines) and by neural microvascular endothelial cells (NMVEC) (3 of 3 lines). SF stimulated the proliferation of glioblastoma and NMVEC cell lines by paracrine or autocrine mechanisms. Conditioned medium (CM) from both glioblastoma and NMVEC cells contained SF-inducing factor (SF-IF) activity, defined by its ability to stimulate SF production in an indicator cell line (MRC5 human fibroblasts). This activity consisted of a high-molecular-weight (> 30 kDa), heat-sensitive component and a low-molecular weight (< 30 kDa), heat-stable component. Furthermore, glioblastoma CM stimulated NMVEC SF production, and NMVEC CM stimulated glioblastoma cell SF production, by 3- to 6-fold in each case. Our findings demonstrate that SF-dependent interactions between glioma cells, and between glioma cells and endothelium, can contribute to the heterogeneous proliferative and angiogenic phenotypes of malignant gliomas in vivo.
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PMID:Scatter factor expression and regulation in human glial tumors. 876 May 95

Scatter factor (SF), also known as hepatocyte growth factor, is angiogenic in systemic tissue, and SF titers correlate with the malignancy and metastatic phenotype of certain systemic cancers. Human gliomas express SF and its receptor c-met, but their role in the malignant progression of these tumors has not been defined. To examine this, 9L glioma cells that express c-met but not SF were transfected with human SF cDNA, and their behavior in vitro and in vivo was examined. SF gene expression was detected in conditioned medium of 9L-SF but not in control 9L-neo-transfected cell lines, by reverse transcriptase-PCR, immunoblot, ELISA, and scatter activity assays. Gliomas derived from 9L-SF and control 9L-neo cell lines implanted in the caudate/putamen of Fisher 344 rats (intracranially) and in the flanks of SCID/Beige mice (subcutaneously) were examined. Extracts from intracranial (i.c.) gliomas contained elevated levels of SF protein as determined by ELISA (1 to 5.5 ng SF/mg protein), whereas no SF was detected in control tumors. Reverse transcriptase-PCR of RNA from i.c. gliomas revealed that only 9L-SF gliomas expressed SF and both 9L-neo and 9L-SF gliomas expressed the c-met SF receptor. By postimplantation Day 14, 9L-SF i.c. gliomas were approximately 5-fold larger than 9L-neo control tumors (p < 0.001). Subcutaneous 9L-SF glioma growth was also greater than that in controls, although the differences were more variable. SF-producing i.c. gliomas contained elevated levels of 48-kd urokinase (3.5-fold) and 92-kd type IV collagenase (2.8-fold), both enzymes that correlate with the malignant progression of human gliomas (p < 0.001). SF-producing and control 9L cell lines did not differ in rates of proliferation, thymidine incorporation, or adhesion-independent growth in vitro. Conditioned medium from 9L-SF cells stimulated thymidine incorporation into microvessel brain endothelial cells 3- to 4-fold higher than did CM from 9L-neo controls (p < 0.001). Intracranial 9L-SF gliomas were more angiogenic than controls based on elevated peak (2.25-fold; p < 0.005) and mean (1.7-fold; p < 0.008) blood vessel densities. These results suggest that SF production by glioma cells enhances glioma malignancy in vivo, in part, by paracrine mechanisms involving glioma-associated angiogenesis.
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PMID:Scatter factor/hepatocyte growth factor gene transfer enhances glioma growth and angiogenesis in vivo. 911 17

Invasive proliferation is a critical biological characteristic of gliomas. We evaluated the activities of hepatocyte growth factor (HGF) on proliferation and motility of glioma cells, comparing them with the effects of other growth factors (EGF, bFGF, PDGF-BB, TGF-beta 1). Seven primary culture lines all expressed c-met and HGF mRNA, and secreted HGF. HGF stimulated 3H-thymidine uptake of every glioma cell line (30 to 70% upregulation). Boyden chamber assay and scattering assay revealed that HGF promoted cell motility with chemokinetic and strong chemotactic activities. Concentric circle assay showed that HGF promoted two-dimensional expansion (proliferation and motility) most strongly among the growth factors studied. Further, we analyzed 23 paraffin-embedded sections of surgically resected gliomas (7 grade II, 8 grade III, and 8 grade IV) by immunohistochemistry. Expression of HGF and Met increased with malignant progression of gliomas, suggesting that gliomas stimulated their invasive proliferation by autocrine HGF production. Neurons and vasculature were HGF-positive, and Met-positive glioma cells gathered around them. The data indicate that neurons and vasculature, which are the main tracks of glioma invasion, augment chemotactic invasion and proliferation of gliomas by paracrine HGF secretion. Clearly HGF plays a critical role in invasive proliferation of glioma cells and it is therefore a candidate target of therapeutic intervention.
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PMID:Modulation of motility and proliferation of glioma cells by hepatocyte growth factor. 926 34

Using double immunofluorescence staining and quantitative confocal laser scan microscopy, we show that the intensity of hepatocyte growth factor/scatter factor (HGF/SF) and Met staining in human primary brain tumors increases with the grade of malignancy and is prevalent in both the infiltrating tumor cells and endothelial hyperplastic areas. HGF/SF and Met also are expressed in vitro in glioblastoma multiforme cell lines as well as in normal human astrocyte (NHA) cells. Moreover, HGF/SF stimulates tyrosine phosphorylation of Met in both glioma cell lines and NHA cells, but only the glioma cell lines proliferate and become motile and invasive in response to HGF/SF, whereas the NHA cells are nonresponsive. These results implicate autocrine/paracrine Met-HGF/SF signaling in glioma tumorigenesis and suggest that HGF/SF signaling through Met is negatively regulated in NHA cells.
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PMID:Met and hepatocyte growth factor/scatter factor expression in human gliomas. 939 65

Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchyme-derived cytokine that stimulates motility and invasiveness of epithelial and cancer cells. These responses are transduced through the c-met proto-oncogene product, a transmembrane tyrosine kinase that functions as the HGF/SF receptor. We have shown that HGF/SF is a potent angiogenic molecule and that its angiogenic activity is mediated primarily through direct actions on vascular endothelial cells. These include stimulation of cell migration, proliferation, protease production, invasion, and organization into capillary-like tubes. We further showed that HGF/SF is overexpressed in invasive human cancers, including breast cancer, relative to non-invasive cancers and benign conditions. In invasive breast cancers, the content of HGF/SF is strongly correlated with that of von Willebrand's factor, a marker of vascular endothelial cells. Furthermore, transfection of breast cancer and glioma cell lines with HGF/SF cDNA greatly enhanced the ability of these cells to grow as tumours in orthotopic sites in syngeneic or immunocompromized host animals. The increased growth rate of the HGF/SF-transfected cells was attributable, in part, to increased tumour angiogenesis. These findings suggest that HGF/SF may function as a tumour progression factor, in part by stimulating tumour cell invasiveness and in part by stimulating angiogenesis.
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PMID:HGF/SF in angiogenesis. 952 73

Hepatocyte growth factor/scatter factor (HGF/SF), which has various physiological functions, and its receptor c-Met, the human c-met proto-oncogene product, are thought to be determinant in the pathological processes of various malignancies. To investigate the possible role of HGF/SF in the progression of development of astrocytic tumors, we examined the expression of c-Met in these tumors. Immunohistochemistry using the streptavidin-biotin peroxidase complex method and immunofluorescence double staining with anti-c-Met polyclonal and anti-glial fibrillary acidic protein monoclonal antibodies were performed. Positive c-Met expression was detected in 31 of the 42 astrocytic tumors and some of the control cases analyzed. c-Met-positive cells showed morphological characteristics of astrocytes. Especially in the cases of high-grade tumors, c-Met positivity was abundant in cells in both vascular-rich and peripheral regions of the tumors but not in the cells with distinctly malignant features. Immunofluorescence double staining revealed that the c-Met-positive cells were in part of astrocytic origin. We suggest that c-Met-positive cells are affected by some factors in the lesions where the pathological processes are in a state of development. Our studies indicated that c-Met expression might take part in glioma invasion but not in the development of malignancy.
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PMID:Immunohistochemical examination of c-Met protein expression in astrocytic tumors. 956 11

Recent findings suggest that hepatocyte growth factor/scatter factor (HGF/SF) contributes to the malignant progression of human gliomas. We investigated the effect of HGF/SF on vascular endothelial growth factor (VEGF) expression of c-Met/HGF receptor-positive human glioma cell lines. Treatment of the glioma cells with various concentrations of HGF/SF resulted in an enhanced secretion of VEGF proteins accompanying increased transcription of VEGF mRNA in a dose-dependent fashion. Since malignant gliomas frequently co-express HGF/SF and its receptor, these results suggest that HGF/SF could act as an indirect angiogenic factor through autocrine induction of VEGF expression and secretion in malignant gliomas.
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PMID:Up-regulation of vascular endothelial growth factor induced by hepatocyte growth factor/scatter factor stimulation in human glioma cells. 970 34

Angiogenesis is a possible target in the treatment of human gliomas. To evaluate the role of 3 growth factors, vascular endothelial growth factor (VEGF), hepatocyte growth factor/scatter factor (HGF/SF) and basic fibroblast growth factor (bFGF), in the angiogenic cascade, we determined their levels in extracts of 71 gliomas by enzyme-linked immunosorbent assay (ELISA). The levels of bFGF were only marginally different between gliomas of World Health Organization (WHO) grade II (low grade) and grades III and IV (high grade). In contrast, the mean concentrations of VEGF were 11-fold higher in high-grade tumors and those of HGF/SF 7-fold, respectively. Both were highly significantly correlated with microvessel density (p < 0.001) as determined by immunostaining for factor VIII-related antigen. In addition, VEGF and HGF/SF appeared to be independent predictive parameters for glioma microvessel density as determined by multiple regression analysis. We measured the capacity of all 3 factors to induce endothelial tube formation in a collagen gel. In this assay, bFGF was found to be an essential cofactor with which VEGF as well as HGF/SF were able to synergize independently. According to the concentrations of angiogenic factors, extracts from high-grade tumors were significantly more potent in the tube formation assay than the low-grade extracts (p = 0.02). Adding neutralizing antibodies to bFGF, VEGF and HGF/SF together with the extracts, tube formation was inhibited by up to 98%, 62% and 54%, respectively. Our findings suggest that bFGF is an essential cofactor for angiogenesis in gliomas, but in itself is insufficient as it is present already in the sparsely vascularized low-grade tumors. Upon induction of angiogenesis in high-grade tumors, bFGF may synergize with rising levels of not only VEGF but possibly also with HGF/SF, which appears here to be an independent angiogenic factor.
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PMID:Levels of vascular endothelial growth factor, hepatocyte growth factor/scatter factor and basic fibroblast growth factor in human gliomas and their relation to angiogenesis. 998 25


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