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

The 9L rat glioma cells grown in culture, when subjected to a mechanical injury (scratch wound) and/or a chemical injury (CdCl2) manifest changes which are characteristic of an astrocyte reaction (astrogliosis) in the central nervous system. Such changes include cell hypertrophy and an increase in immunostaining for the astrocytic marker proteins, glial fibrillary acidic protein and J1-31 antigen. Mitochondria also increase in size and number, and the endoplasmic reticulum expands in area. These mechanical and chemical injuries are coordinated, and act synergistically to induce a considerably more intense astroglial reaction by 9L cells than can be elicited with either injurious agent alone, and this occurs without any interactions with microglia, neurons or oligodendroglia. The phenomenon suggests that more than one transcriptional mechanism is involved in the activation of astrocytes, and that mechanical and CdCl2-induced injuries, respectively, probably affect different receptors and second- and third-messenger pathways. There are a number of questions concerning the molecular biology of reactive astrocytes which can be addressed through the use of the 9L rat glioma cell model. This model offers certain advantages over primary cultures of astrocytes, namely a low basal level of reactivity (because the cells are not subjected to mechanical injury prior to experimentation), an absence of contaminating microglial cells, greater ease of reproducibility of results, lower costs and avoidance of the use of animals.
 ...
PMID:Up-regulation of reactive astrogliosis in the rat glioma 9L cell line by combined mechanical and chemical injuries. 936 21

Gliomas are the most frequently diagnosed adult primary brain malignancy. These tumors have a tendency to invade diffusely into the surrounding healthy brain tissue, thereby precluding their successful surgical removal. In this report, we examine the potential for the neuregulin-1/erbB receptor signaling network to contribute to this process by modulating glioma cell motility. Neuregulin-1 is expressed throughout the immature and adult central nervous system and has been demonstrated to influence the migration of a variety of cell types in the developing brain. In addition, erbB2, an integral member of the heterodimeric neuregulin-1 receptor, has been shown to be overexpressed in human glioma biopsies. Using antibodies specific for erbB2 and erbB3, we show that these receptors localize preferentially in regions of the plasma membrane which are involved in facilitating cellular movement. Here, erbB2 colocalizes and coimmunoprecipitates with members of the focal complex including beta1-integrin and focal adhesion kinase. Further, erbB receptor activation by neuregulin-1 enhances cell motility in two-dimensional scratch motility assays and stimulates cell invasion in three-dimensional Transwell migration assays. These effects of neuregulin-1 appear to involve the activation of focal adhesion kinase, which occurs downstream from erbB2 receptor stimulation. Taken together these data suggest that neuregulin-1 plays an important modulatory role in glioma cell invasion.
 ...
PMID:Neuregulin-1 enhances motility and migration of human astrocytic glioma cells. 1260 Sep 89

The aim of this study was to explore the potential role of AKT2 in glioma cell invasion. Therefore, dominant-negative (DN-AKT2) and antisense AKT2 constructs (AS-AKT2) were transfected into rat C6 glioma cells with elevated endogenous AKT2 expression. In situ hybridization and Western blot analysis were used to identify AKT2 expression. Spheroid culturing was used to assess cell migration and invasion in Matrigel from spheroids. Cell motility and invasion were also evaluated by scratch and Transwell invasion assays, respectively. The secretion of matrix metalloproteinases (MMPs), MMP2 and MMP9, was determined by gelatin zymography. AKT2 expression was inhibited in C6 cells transfected with AS-AKT2 but did not significantly change in cells transfected with DN-AKT2. The cell migration distance from spheroids or the number of cells migrating into the acellular space created by scratching was reduced in cells transfected with DN-AKT2 or AS-AKT2 compared to the control cells. The invasive distance of cells from the spheroids in Matrigel sandwich and the number of invading cells through the Matrigel were also decreased in the DN-AKT2- and AS-AKT2-transfected cells. Gelatin zymography showed that the production of MMP2 and MMP9 was inhibited in transfected cells. In conclusion, AKT2 plays an important role in glioma cell motility and invasion. Therapy based on AKT inhibition may complement currently available treatment to control glioma cell invasion.
 ...
PMID:Antisense and dominant-negative AKT2 cDNA inhibits glioma cell invasion. 1555 54

A key regulatory mechanism in cell motility is the control of myosin activity, which in non-muscle cells is determined by phosphorylation of the myosin regulatory light chain (MRLC). Here we show that MRLC-interacting protein (MIR)-interacting saposin-like protein (MSAP) enhances cell spreading in fibroblasts and migration of rat C6 glioma cells through increases in MRLC phosphorylation. Overexpression of MSAP enhanced the motility of glioma cells measured in matrigel invasion chambers and using a scratch assay. Downregulation of MSAP by RNA interference significantly decreased glioma cell migration and phosphorylation of MRLC. Inhibition of the corresponding MRLC kinase by ML-7 did not affect migration of MSAP-overexpressing cells. The present results show that MSAP controls glioma cell migration via enhancement of MRLC phosphorylation. This effect is independent of the activity of MRLC kinase. Thus, MSAP is a novel modulator of cell motility that influences migration of glioma cells and possibly other tumors.
 ...
PMID:MSAP enhances migration of C6 glioma cells through phosphorylation of the myosin regulatory light chain. 1590 59

Versican is a large chondroitin sulphate proteoglycan produced by several tumour cell types, including high-grade glioma. The increased expression of certain versican isoforms in the extracellular matrix (ECM) plays a role in tumour cell growth, adhesion and migration. Transforming growth factor-beta2 (TGF-beta2) is an important modulator of glioma invasion, partially by remodeling the ECM. However, it is unknown whether it interacts with versican during malignant progression of glioma cells. Here, we analysed the effect of TGF-beta2 on the expression of versican isoforms. The expression of versican V0/V1 was upregulated by TGF-beta2 detected by quantitative polymerase chain reaction and immunoprecipitation, whereas V2 was not induced. Using time-lapse scratch and spheroid migration assays, we observed that the glioma migration rate is significantly increased by exogenous TGF-beta2 and inhibited by TGF-beta2-specific antisense oligonucleotides. Interestingly, an antibody specific for the DPEAAE region of glycosaminoglycan-beta domain of versican was able to reverse the effect of TGF-beta2 on glioma migration in a dose-dependent manner. Taken together, we report here that TGF-beta2 triggers the malignant phenotype of high-grade gliomas by induction of migration, and that this effect is, at least in part, mediated by versican V0/V1.
 ...
PMID:The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-beta2. 1745 2

Our results demonstrate the first findings of expression and function of the purinergic P2X7 receptor (P2X7R) in rat C6 glioma cells. P2X7R mRNA and protein were present in unstimulated C6 cells and were up-regulated by cell exposure to the P2X7R agonist, 2',3'-(benzoyl-4-benzoyl)-ATP (BzATP). Activation of P2X7R in C6 in response to BzATP led to increased mobilization of intracellular calcium [Ca2+]i and formation of large pores. Chronic exposure of C6 cells to BzATP enhanced the expression of pro-inflammatory factors including MCP-1, IL-8 and VEGF. In a scratch-wound migration assay, the P2X7R was shown to regulate cell mobility. The overall results suggest that P2X7R activation in C6 is linked with increased pro-inflammatory factors and tumor cell migration.
 ...
PMID:Expression and function of the P2X(7) receptor in rat C6 glioma cells. 1803 56

In vitro cell imaging is a useful exploratory tool for cell behavior monitoring with a wide range of applications in cell biology and pharmacology. Combined with appropriate image analysis techniques, this approach has been shown to provide useful information on the detection and dynamic analysis of cell events. In this context, numerous efforts have been focused on cell migration analysis. In contrast, the cell division process has been the subject of fewer investigations. The present work focuses on this latter aspect and shows that, in complement to cell migration data, interesting information related to cell division can be extracted from phase-contrast time-lapse image series, in particular cell division duration, which is not provided by standard cell assays using endpoint analyses. We illustrate our approach by analyzing the effects induced by two sigma-1 receptor ligands (haloperidol and 4-IBP) on the behavior of two glioma cell lines using two in vitro cell models, i.e., the low-density individual cell model and the high-density scratch wound model. This illustration also shows that the data provided by our approach are suggestive as to the mechanism of action of compounds, and are thus capable of informing the appropriate selection of further time-consuming and more expensive biological evaluations required to elucidate a mechanism.
 ...
PMID:Videomicroscopic extraction of specific information on cell proliferation and migration in vitro. 1859 94

Beta1,4-Galactosyltransferases (beta1,4-GalTase) exposed on the cell surface are involved in cell migration. Specifically, beta1,4-GalTase V is highly expressed in glioma and promotes invasion, growth, and survival of glioma cells. A glycocalix[8]arene exposing N-acetylglucosamine (GlcNAc) residues (compound 1) inhibited rat C6 glioma cell migration as assessed in a scratch wound model. This effect was related to inhibition of focal adhesion kinase phosphorylation, measured by western blot analysis, and specifically observed in the area bordering the scratch wound. Compound 1 inhibited also C6 cell proliferation, an effect unrelated to its ability to interact with GalTase as it was mimicked by different calix[8]arene derivatives, all characterized by multivalency and ureido groups. Compound 1 did not induce apoptotic death, but caused a different distribution of C6 cells within the cell cycle. The results here reported identify compound 1 as a molecule able to exert inhibitory effects on C6 cell migration and proliferation, independently, because of distinct components in its structure.
 ...
PMID:Inhibition of rat glioma cell migration and proliferation by a calix[8]arene scaffold exposing multiple GlcNAc and ureido functionalities. 1877 7

The cell-surface receptor protein tyrosine phosphatase mu (PTPmu) is a homophilic cell adhesion molecule expressed in CNS neurons and glia. Glioblastomas (GBMs) are the highest grade of primary brain tumors with astrocytic similarity and are characterized by marked dispersal of tumor cells. PTPmu expression was examined in human GBM, low-grade astrocytoma, and normal brain tissue. These studies revealed a striking loss of PTPmu protein expression in highly dispersive GBMs compared to less dispersive low-grade astrocytomas and normal brain. We hypothesized that PTPmu contributes to contact inhibition of glial cell migration by transducing signals in response to cell adhesion. Therefore, loss of PTPmu may contribute to the extensive dispersal of GBMs. The migration of brain tumor cells was assessed in vitro using a scratch wound assay. Parental U-87 MG cells express PTPmu and exhibited limited migration. However, short-hairpin RNA (shRNA)-mediated knockdown of PTPmu induced a morphological change and increased migration. Next, a brain slice assay replicating the three-dimensional environment of the brain was used. To assess migration, labeled U-87 MG glioma cells were injected into adult rat brain slices, and their movement was followed over time. Parental U-87 MG cells demonstrated limited dispersal in this assay. However, PTPmu shRNA induced migration and dispersal of U-87 MG cells in the brain slice. Finally, in a mouse xenograft model of intracranially injected U-87 MG cells, PTPmu shRNA induced morphological heterogeneity in these xenografts. Together, these data suggest that loss of PTPmu in human GBMs contributes to tumor cell migration and dispersal, implicating loss of PTPmu in glioma progression.
 ...
PMID:PTPmu suppresses glioma cell migration and dispersal. 1930 59

The LGI1 gene suppresses invasion in glioma cells and predisposes to epilepsy. In a gene expression array comparison between parental cells and T98G cell clones forced to express LGI1, we demonstrate that the canonical axon guidance pathway is the most significantly affected. In particular, aspects of axon guidance that involve reorganization of the actin cytoskeleton, which is also involved in cell movement and invasion, were affected. Analysis of actin fiber organization using fluorescence microscopy demonstrated that different T98G cell clones expressing the exogenous LGI1 gene show high levels of stress fibers compared with controls. Since stress fiber formation is associated with loss of cell mobility, we used scratch wound assays to demonstrate that LGI1-expressing clones show a significant reduction in cell mobility. LGI1 reexpression also resulted in loss of the PDGFRA and EGFR proteins, suggesting a rapid turnover of these receptors despite increased mRNA levels for PDGFRA. LGI1 suppression of invasion is associated with loss of ERK/MAPK1 activation. LGI1 is a secreted protein, and when the culture supernatant from cells expressing FLAG- and GFP-tagged proteins were applied to parental T98G cells, ERK/MAPK1 phosphorylation and cell mobility was suppressed, demonstrating that the LGI1 protein acts as a suppressive agent for cell movement in this assay. These observations support a previous suggestion that LGI1 can reduce cellular invasion in in vitro assays and, as a secreted agent, may be developed as a means of treating metastatic cancer. In addition, this observation provides a mechanistic link for LGI1's common role in metastasis and epilepsy development.
 ...
PMID:Reexpression of LGI1 in glioma cells results in dysregulation of genes implicated in the canonical axon guidance pathway. 1983 47


1 2 3 4 5 6 7 8 9 Next >>