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)

The aim of the study was to assess the differential intra- and intertumoral heterogeneity and patterns of matrix metalloproteinase expression in human glioblastomas in vivo. 12 glioblastoma samples were analyzed for MMP expression by semi-quantitative RT-PCR. A total of 56 samples (8 adjoining regions of 6 glioblastoma tumors) were immunohistochemically examined for the expression and regional distribution of gelatinase-A (MMP-2), gelatinase-B (MMP-9), matrilysin (MMP-7) and stromelysin-1 (MMP-3). Gelatinase-A mRNA was detected in all samples, gelatinase-B was found in numerous samples. Correspondingly, strong expression levels of both gelatinase protein was seen in immunohistochemistry. Gelatinase-A was expressed by both tumor cells and endothelium while gelatinase-B was found to be restricted to endothelial cells. Stromelysin-1 protein was not detected in any of the samples. Matrilysin was found around tumor cells of three samples from one patient only. The strong immunoreactivity seen for gelatinase-A around tumor cells and blood vessels suggests a role in both tissue degradation and tumor neoangiogenesis which is in accordance with previously published in vitro data. The marked localization of gelatinase-B to the endothelium and its presence in non-infiltrative benign lesions, however, makes a direct proteolytic role of gelatinase-B on ECM components during glioma invasion appear unlikely. Its close association with vascular structures, however, might indicate a link to neoangiogenesis. The significance of matrilysin which was only seen in tumor cells in three samples remains unclear. Stromelysin-1, though strongly expressed in cell lines, does not appear to play a role in glioblastoma tumors in vivo.
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PMID:Heterogeneous regional expression patterns of matrix metalloproteinases in human malignant gliomas. 1057 6

Matrix metalloproteinases (MMPs) are a growing family of zinc-dependent endopeptidases that are capable of degrading various components of the extracellular matrix. These enzymes have been implicated in a variety of physiological and pathological conditions including embryogenesis and tumour invasion. The synthesis of many MMPs is thought to be regulated by growth factors, cytokines and hormones. In this study, we investigated the effects of five exogenous growth factors known to be expressed by gliomas [epidermal growth factor (EGF), basic growth factor (bFGF), transforming growth factor beta (TGF-beta1,2) and vascular endothelial growth factor (VEGF)].on MMP-2 and MMP-9 expression in an ependymoma, two grade III astrocytomas, a grade III oligoastrocytoma and a benign meningioma. Zymogram analysis revealed that the effects of the growth factors depended upon the cell lines used in the study. Growth factors generally up-regulated MMP-2 and MMP-9 expression in the gliomas but were least effective in the meningioma; the effect being most prominent with TGF-beta1 and TGF-beta2 in all the cell lines. It is hypothesized that paracrine growth factor interplay may be crucial in the regulation of MMP expression by glioma invasion of the normal brain.
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PMID:The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumour cells. 1063 66

In tumor tissue specimens of 27 primary and 17 secondary glioblastomas and the precursor lesions, the immunohistochemical expression patterns of the membrane protein CD44s, the basal lamina proteins laminin, collagen IV, and fibronectin, the lectin galectin-3 recognizing tenascin and N-CAM as well as of the matrix-degrading enzymes matrix metalloproteinase MMP-2 and MMP-9, and cathepsin D were studied. Besides expression of basal lamina proteins in vessels, all glioblastomas and the precursor lesions showed strong immunoreactivity of CD44s, tenascin, galectin-3, and N-CAM which were restricted to solid tumor masses. Present in solid tumor areas, MMP-2, MMP-9 and cathepsin D were also strongly expressed by single tumors cells invading adjacent brain tissue at the infiltrative margin. Neither the expression pattern in primary and secondary glioblastomas nor in the precursor tumors revealed significant differences. There was also no intraindividual constant expression pattern during glioma progression or correlation with malignancy. Restricted expression of CD44s, galectin-3, tenascin and N-CAM in solid tumor masses seems to contribute to homotypic tumor cell adhesion while single tumor cells abolish this expression profile and acquire invasive activities by expression of cathepsin D, MMP-2 and MMP-9.
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PMID:Expression of adhesion factors and degrading proteins in primary and secondary glioblastomas and their precursor tumors. 1072 72

It has been reported that matrix metalloproteinases (MMPs) are highly expressed in malignant glioma cells and that this increased expression may facilitate the invasiveness of tumor cells. The authors investigated the expression and enzymatic activity of MMPs in rat brain during the growth of malignant gliomas at different time intervals. C6 rat glioma cells were unilaterally implanted into rat cerebral hemispheres. After 7 or 14 days, these brain tissues were prepared for SDS-PAGE zymography, Western blotting, immunohistochemistry, and in situ zymography. SDS-PAGE zymography and Western blotting revealed that the expression of proMMP-2 in rat brains with C6 glioma cells was significantly higher than that in normal or the sham-operated rat brains, and that the activated form of MMP-2 was detected only in the former but not in the latter. On immunohistochemistry, C6 glioma cells presenting invasive growth into the rat brain parenchyma and vessels demonstrated MMP-2 immunoreactivity. On in situ zymography, foci of invasive C6 glioma cells in rat brain tissue showed gelatinolytic activity. These results suggest that expression and activation of MMP-2 may be one of the crucial steps for glioma cell invasion into the brain parenchyma in vivo.
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PMID:The expression and activation of matrix metalloproteinase-2 in rat brain after implantation of C6 rat glioma cells. 1089 63

To evaluate possible roles of matrix metalloproteinase (MMP)-1, -2, tissue inhibitor of metalloproteinase (TIMP)-1, -2 and membrane-type-1 matrix metalloproteinase (MT1-MMP) in invasion of human gliomas, expressions of these proteins were investigated in ten cases of human glioma and two meningioma tissues and eight human glioma cell lines. In gelatin zymography, MMP-2 activities of glioblastomas were higher than astrocytomas. The activated form of MMP-2 was seen in five of six cases of glioblastomas, but not in astrocytomas. MMP-9 activity was detected in all cases of malignant astrocytomas but the reactivity of MMP-9 was weaker than that of MMP-2. MT1-MMP mRNA expression in glioblastomas was higher than that in astrocytomas. Five cases of glioblastomas with activated form of MMP-2 had MT1-MMP expressions. In vitro, human glioma cell lines with high expression of MT1-MMP also showed high MMP-2 activity. TIMP-1 transcripts were constitutively present in almost all glioma tissues and cell lines, whereas TIMP-2 mRNA were weak especially in malignant gliomas. Imbalance of TIMP-2/MMP-2 was observed using immunoprecipitation analysis in a glioma cell line. High expression of MMP-2 and MT1-MMP is possibly involved in invasiveness of malignant glioma.
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PMID:Matrix metalloproteinases in human gliomas: activation of matrix metalloproteinase-2 (MMP-2) may be correlated with membrane-type-1 matrix metalloproteinase (MT1-MMP) expression. 1089 74

Structural changes in the extracellular matrix (ECM) are necessary for cell migration during tissue remodeling and local neoplastic cell invasion. The matrix metalloproteinases (MMPs) and their inhibitors have been shown to be critical modulators of ECM composition and are thus, crucial in tumor cell invasion and metastasis. The immunocytochemical profile of MMP-2, -3, -9, -10, and -13 expression was observed in 24 primary human childhood astrocytomas (ASTRs) employing an indirect alkaline phosphatase conjugated antigen detection technique. Evaluation of the results was based on (a) the percent of neoplastically transformed cells that reacted positively and (b) a measure of staining intensity [graded from A (highest) to D (negative)]. The two forms of stromelysin, MMP-3 and -10, share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Strong overall expression of MMP-3 and -10 was found in ASTRs, especially in the ECM adjacent to blood vessels. Positive immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90% of the neoplastically transformed cells (+4) and the staining intensity was also the strongest possible (A,B). No immunoreactivity was detected using antibodies directed against MMP-2, -9, and -13. Based on these results, MMP-3 and -10 are implicated in the pathogenesis of pediatric ASTRs. Further characterization of the expression and utilization of MMPs and their inhibitors in the progression of ASTRs may establish differential regulation and utilization of the various MMPs during the progression of glial tumors, from low-grade pilocytic ASTR to high-grade glioblastoma multiforme.
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PMID:Matrix metalloproteinase expression in childhood astrocytomas. 1106 55

This study aims at the in situ identification of factors mediating glioma cell invasion requiring adhesion, extracellular matrix degradation, and migration. Forty-five gliomas (astrocytomas, glioblastomas, oligodendrogliomas, and mixed gliomas) were investigated for the immunohistochemical expression of the membrane protein CD44s, the basal lamina proteins laminin, collagen IV, and fibronectin, the lectin galectin-3 recognizing tenascin and N-CAM, as well as for the matrix-degrading enzymes metalloproteinases MMP-2, MMP-9, and cathepsin D. Besides vessels expressing basal lamina proteins, tenascin, MMP-2, MMP-9, and galectin-3, tumor cells revealed strong immunoreactivity for CD44s, tenascin, galectin-3, and N-CAM, which was restricted to solid tumor masses. Single invading cells displayed distinct expression of MMP-2 and MMP-9, also found in solid tumor areas, as well as of cathepsin D. Restricted expression of CD44s, galectin-3, tenascin, and N-CAM in solid tumor masses seems to contribute to homotypical tumor cell adhesion. However, switching to an invasive phenotype, single tumor cells lack this expression pattern and acquire degrading and phagocytic activities by expressing cathepsin D, MMP-2, and MMP-9, which are also expressed by solid tumor masses facilitating the loosening and invasion of single neoplastic cells. The blocking of these factors may be of potential benefit in anti-invasive therapy.
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PMID:Adhesive and invasive features in gliomas. 1108 57

Matrix metalloproteinase (MMP) has come to be highlighted by its close relation to the cell invasion of gliomas. Suppression of MMP activity in malignant glioma cells would be meriting to local delivery of genes or chemotherapeutic agents. In this study, we employed a novel MMP inhibitor, SI-27 to investigate inhibition of cell invasiveness in human malignant glioma cell lines, U87MG, U251MG, and U373MG. We evaluated with zymogram, reverse zymogram, and cell invasion assay after exposure of SI-27 for 24 h followed by preliminary MTT assay to find non-cytotoxic dose range, 5, 10, 50, 100 microg/ml compared with non-treatment group as the control. Common to three glioma cell lines, zymogram disclosed that expressions of MMP-2 and -9 were suppressed in a dose-dependent fashion, meanwhile those of tissue inhibitor of MMP (TIMMP) in reverse zymogram were not. The numbers of invading cells through Boyden chamber were significantly reduced in a dose-dependent manner, while those with 5 microg/ml were not diminished common to those three lines. In conclusion, dose concentration ranging 10-100 microg/ml of SI-27 inhibited MMP-2 and -9 mediated cell invasiveness in malignant glioma cell lines. This is the first report for chemotherapeutic effect of SI-27 on glioma cells.
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PMID:Suppression of cell invasion on human malignant glioma cell lines by a novel matrix-metalloproteinase inhibitor SI-27: in vitro study. 1110 Aug 19

In the present work, we analyzed the expression of two major components of the extracellular matrix (ECM), laminin and fibronectin and of two related matrix-metalloproteinases, MMP-2 and MMP-9, in three human glioma cell lines (8 MG, 42 Mg and GL-15) in relation with their differential invasive properties. Immunocytochemistry and Western-blots assays indicated the presence of a 200 kDa laminin, similarly expressed in the three cell lines but undetectable in their ECM. In the opposite, a 230 kDa fibronectin, detected in the three cell lines was differently expressed and only observed in the ECM of the less invasive 8 and 42 MG cells. MMP-2 mRNA analyzed by Northern blots and proMMP-2, evaluated by zymography, were found in the three cell lines but were both ten times higher in the most invasive GL-15 cells. In addition, the active form of MMP-2 was only found in the GL-15 cells. In the opposite, the expression of specific tissular inhibitor (TIMP)-2, an endogenous MMP-2 inhibitor, was restricted to the less invasive cells. MMP-9 activity was detected only in the 8 and 42 MG cells and may not be directly involved in invasion. Taken together, these results indicate that a high MMP-2/TIMP-2 ratio may be responsible for the absence of extracellular fibronectin, underlining the participation of tumour cells in the proteolytic degradation of the ECM. An unbalanced MMP-2/TIMP-2 ratio in the micro-environment of malignant cells may contribute to their invasive properties.
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PMID:Differential expression of laminin and fibronectin and of their related metalloproteinases in human glioma cell lines: relation to invasion. 1116 57

Characteristics of human malignant glioma are excessive proliferation, infiltrative growth, angiogenesis and suppression of anti-tumor immune surveillance. Transforming growth factor-beta (TGF-beta), a versatile cytokine, is intimately involved in the regulation of these processes. Here, we discuss the interactions of TGF-beta with growth factors, such as basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and platelet derived growth factor (PDGF), metalloproteinases (MMP-2, MMP-9) and their inhibitor, plasmin activator inhibitor-1 (PAI-1), and immune cells, like natural killer cells, T-cells and microglia. The differential effects of TGF-beta in glioma biology are outlined with emphasis on the induction of a survival advantage for glioma cells by enforced cell growth, migration, invasion, angiogenesis and immune paralysis. By virtue of its growth regulatory and immunomodulatory properties, TGF-beta promises to become a novel target for the experimental therapy of human malignant glioma.
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PMID:Malignant glioma biology: role for TGF-beta in growth, motility, angiogenesis, and immune escape. 1117 Feb 99


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