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)

Myosin has been isolated from the clonal lines of murine neuroblastoma and rat glioma cells. Partial characterization of the two cellular myosins indicates that both possess the following properties: (1) the same elution position as rabbit skeletal muscle myosin by Sepharose 4B chromatography; (2) the presence of heavy (molecular weight about 200,000) and light subunit polypeptides by sodium dodecyl sulfate polyacrylamide gel electrophoresis; (3) EDTA and Ca2+ activated but Mg2+-inhibited ATPase activity in 0.6 M KCl; and (4) binding to rabbit skeletal muscle F-actin which is inhibited by Mg2+-ATP. For both mouse neuroblastoma and rat glioma cells, approximately 0.5-1.5% of the total cell protein is present as myosin. Cellular myosin appears to be indistinguishable in quantity and biochemical properties regardless of whether it is isolated from monolayer or suspension neuroblastoma cells.
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PMID:Isolation and characterization of myosin from cloned rat glioma and mouse neuroblastoma cells. 13 25

The pathological findings, including immunohistochemical and electron microscopical findings, in three infants who died unexpectedly of cardiac tumor or cardiomyopathy are reported. The first was a 13-month-old boy with tuberous sclerosis and multiple rhabdomyomas of the heart, who presented with a postpartal cardiac murmur and moderate cardiomegaly. The further history was unknown. The rhabdomyoma nodules were composed of spider cells containing small amounts of desmin and myosin as well as isolated myofibrils. Microscopically small glioma nodules contained high amounts of GFAP. The second case, a boy 4 months of age, died of a large benign fibrous histiocytoma of the heart after an uneventful history. Tumor cells contained alpha-1-anti-chymotrypsin and lysozyme. The third case, a girl 2 months of age, died unexpectedly of histiocytoid cardiomyopathy. The affected cells contained fat droplets, glycogen granules, many leptomer myofibrils and small amounts of myosin and desmin.
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PMID:Unexpected infant death attributable to cardiac tumor or cardiomyopathy. Immunohistochemical and electron microscopical findings in three cases. 216 15

C6 Rat glioma cells acquire an astrocyte-like morphology (cytoplasmic shrinking) after exposure to beta-adrenergic compounds (e.g., isoproterenol) in serum-free medium. This morphological response is mediated by elevation of the intracellular cAMP level and possibly by activation of a kinase phosphorylating and inactivating the myosin-L-kinase in analogy to observations with smooth muscle cells. The result is a disturbance of the stress fiber function, which depends on a cooperation between actin and myosin. Diethylstilbestrol (DES) induces an identical morphological response in these cells under serum-free conditions. However, under the influence of DES no increase of the cAMP level was observed. In addition, at concentrations not inducing these morphological responses, DES inhibits the isoproterenol-induced effect when administered simultaneously or prior to the beta-receptor agonist. DES does not inhibit the isoproterenol-mediated morphological response when added after isoproterenol treatment. Furthermore, if serum is added to cells showing the isoproterenol- or DES-mediated astrocyte-like morphology (DES or isoproterenol present all the time) the cells regain their normal fibroblast-like morphology within 30 min. In view of these results the question arises whether DES interferes with myosin-L-chain phosphorylation or whether it directly interacts with the cytoskeleton stress fiber components, as cytochalasin B1 does. Thus it remains to be established whether the observed effects are related to the estrogenic activity of DES. Similar effects were observed with Syrian hamster embryo fibroblasts under the influence of DES and the naturally occurring steroid estrogen 17-beta-estradiol.
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PMID:Does diethylstilbestrol (DES) change the stress fiber organization in C6 rat glioma cells? 285 47

We report the identification and characterization of myr 4 (myosin from rat), the first mammalian myosin I that is not closely related to brush border myosin I. Myr 4 contains a myosin head (motor) domain, a regulatory domain with light chain binding sites and a tail domain. Sequence analysis of myosin I head (motor) domains suggested that myr 4 defines a novel subclass of myosin I's. This subclass is clearly different from the vertebrate brush border myosin I subclass (which includes myr 1) and the myosin I subclass(es) identified from Acanthamoeba castellanii and Dictyostelium discoideum. In accordance with this notion, a detailed sequence analysis of all myosin I tail domains revealed that the myr 4 tail is unique, except for a newly identified myosin I tail homology motif detected in all myosin I tail sequences. The Ca(2+)-binding protein calmodulin was demonstrated to be associated with myr 4. Calmodulin binding activity of myr 4 was mapped by gel overlay assays to the two consecutive light chain binding motifs (IQ motifs) present in the regulatory domain. These two binding sites differed in their Ca2+ requirements for optimal calmodulin binding. The NH2-terminal IQ motif bound calmodulin in the absence of free Ca2+, whereas the COOH-terminal IQ motif bound calmodulin in the presence of free Ca2+. A further Ca(2+)-dependent calmodulin binding site was mapped to amino acids 776-874 in the myr 4 tail domain. These results demonstrate a differential Ca2+ sensitivity for calmodulin binding by IQ motifs, and they suggest that myr 4 activity might be regulated by Ca2+/calmodulin. Myr 4 was demonstrated to be expressed in many cell lines and rat tissues with the highest level of expression in adult brain tissue. Its expression was developmentally regulated during rat brain ontogeny, rising 2-3 wk postnatally, and being maximal in adult brain. Immunofluorescence localization demonstrated that myr 4 is expressed in subpopulations of neurons. In these neurons, prominent punctate staining was detected in cell bodies and apical dendrites. A punctate staining that did not obviously colocalize with the bulk of F-actin was also observed in C6 rat glioma cells. The observed punctate staining for myr 4 is reminiscent of a membranous localization.
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PMID:Rat myr 4 defines a novel subclass of myosin I: identification, distribution, localization, and mapping of calmodulin-binding sites with differential calcium sensitivity. 803 41

Anaplastic gliomas are infiltrative tumors, and their ability to migrate through normal brain contributes to their highly malignant behavior. Invasion of brain requires cell motility, which in turn depends on the activity of the cytoskeleton. A cytoskeletal component central to this process is myosin II, the cytoplasmic analogue of smooth and skeletal muscle myosin. Myosin II activity is regulated by the enzyme myosin light chain kinase, which activates myosin II by phosphorylating it on its regulatory light chain. We have investigated the role of myosin II in glioma motility and invasiveness by examining the effects of two inhibitors of myosin light chain kinase, ML7 and KT5926. Both drugs are potent inhibitors of both glioma motility, as measured by a scrape motility assay, and an in vitro haptotaxis assay. The inhibition of in vitro haptotaxis follows the dose-response relationship expected for competitive inhibition of myosin light chain kinase by these drugs and is seen at drug concentrations that are nontoxic. These results highlight the important role that myosin II contributes to glioma invasiveness and suggest that it may serve as a target in future strategies at blocking invasion by these tumors.
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PMID:Glioma migration can be blocked by nontoxic inhibitors of myosin II. 1023 91

We have studied the effects of the bioactive phospholipid lysophosphatidic acid (LPA) on cell lines derived from highly invasive human glioblastoma multiforme (GBM). Using transwell migration assays, we show that LPA stimulates both chemokinetic and chemotactic migration of glioma cells. Blood brain barrier breakdown and leakage of serum components that most likely include LPA are common features of GBM. Therefore, the effects of LPA on glioma cell motility are intriguing given the fact that, in vivo, GBM cells often migrate great distances from the main tumor, rendering successful therapy extremely difficult. We show here that LPA initiates a variety of signaling cascades in glioma cells. LPA-enhanced transwell migration was sensitive to pertussis toxin (PTX) treatment suggesting an important role for G(i) subtype of G proteins. LPA also stimulated Ca(2+) fluctuations and activation of extracellular signal-regulated kinases (ERKS) 1 and 2, although blocking either pathway had little effect on glioma cell migration. Exposure of glioma cells to LPA resulted in phosphorylation of the regulatory light chain (RLC) of myosin II and the formation of stress fibers and focal adhesions. These effects were blocked by Y-27632, an inhibitor of Rho-activated ROCK kinases. Time-lapse video microscopy revealed that Y-27632-treatment caused cells to assume long thin morphologies that suggested deficiencies in the contractile apparatus. Furthermore, many cells exhibited a conspicuous extension of processes when Rho/ROCK kinase cascades were inhibited. The above results suggest that LPA/Rho signaling cascades play important roles in glioma cell motility and that exposure of tumor cells to LPA in vivo may contribute to their invasive phenotype.
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PMID:Role of lysophosphatidic acid and rho in glioma cell motility. 1070 74

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.
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PMID:MSAP enhances migration of C6 glioma cells through phosphorylation of the myosin regulatory light chain. 1590 59

The role of actin cytoskeleton functional state in glioma C6 cell morphology and calcium signaling was investigated through modification of myosin II activity by blocking Rho-associated kinase with the specific inhibitor Y-27632. Treatment of glioma C6 cells with ROCK inhibitor resulted in actin cytoskeleton reorganization and also in the changed shape and distribution of mitochondria. Changes in the distribution of ER, the main calcium store in glioma C6 cells, were not visible. The inhibition of myosin II activity influences the first phase of calcium signaling evoked by agonist, and both phases of thapsigargin-evoked calcium response. We suggest that the observed increase in Ca2+ release from intracellular stores induced by IP3 formation as well as inhibition of SERCA ATPase is at least in part related to severely affected mitochondria. Enhancement of capacitative calcium entry evoked by thapsigargin is probably associated with the reorganization of the acto-myosin II system. ATP-induced calcium response presents no changes in the second phase. We observed that ATP stimulation of Y-27632 pretreated cells leads to immediate morphological rearrangement of glioma C6 cells. It is a consequence of actin cytoskeleton reorganization: formation of stress fibers and relocation of phosphorylated myosin II to actin filaments. It seems that the agonist-evoked strong calcium signal may be sufficient for myosin II activation and the stress fiber organization. This is the first work showing the dependence between the functional state of the acto-myosin II system and calcium signaling stressing the reversible character of this relationship.
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PMID:Effect of Rho-associated kinase inhibition on actin cytoskeleton structure and calcium response in glioma C6 cells. 1711 79

The ability of gliomas to invade the brain limits the efficacy of standard therapies. In this study, we have examined glioma migration in living brain tissue by using two novel in vivo model systems. Within the brain, glioma cells migrate like nontransformed, neural progenitor cells-extending a prominent leading cytoplasmic process followed by a burst of forward movement by the cell body that requires myosin II. In contrast, on a two-dimensional surface, glioma cells migrate more like fibroblasts, and they do not require myosin II to move. To explain this phenomenon, we studied glioma migration through a series of synthetic membranes with defined pore sizes. Our results demonstrate that the A and B isoforms of myosin II are specifically required when a glioma cell has to squeeze through pores smaller than its nuclear diameter. They support a model in which the neural progenitor-like mode of glioma invasion and the requirement for myosin II represent an adaptation needed to move within the brain, which has a submicrometer effective pore size. Furthermore, the absolute requirement for myosin II in brain invasion underscores the importance of this molecular motor as a potential target for new anti-invasive therapies to treat malignant brain tumors.
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PMID:The role of myosin II in glioma invasion of the brain. 1849 66

Glioblastoma multiforme (GBM) is a malignant astrocytoma of the central nervous system associated with a median survival time of 15 months, even with aggressive therapy. This rapid progression is due in part to diffuse infiltration of single tumor cells into the brain parenchyma, which is thought to involve aberrant interactions between tumor cells and the extracellular matrix (ECM). Here, we test the hypothesis that mechanical cues from the ECM contribute to key tumor cell properties relevant to invasion. We cultured a series of glioma cell lines (U373-MG, U87-MG, U251-MG, SNB19, C6) on fibronectin-coated polymeric ECM substrates of defined mechanical rigidity and investigated the role of ECM rigidity in regulating tumor cell structure, migration, and proliferation. On highly rigid ECMs, tumor cells spread extensively, form prominent stress fibers and mature focal adhesions, and migrate rapidly. As ECM rigidity is lowered to values comparable with normal brain tissue, tumor cells appear rounded and fail to productively migrate. Remarkably, cell proliferation is also strongly regulated by ECM rigidity, with cells dividing much more rapidly on rigid than on compliant ECMs. Pharmacologic inhibition of nonmuscle myosin II-based contractility blunts this rigidity-sensitivity and rescues cell motility on highly compliant substrates. Collectively, our results provide support for a novel model in which ECM rigidity provides a transformative, microenvironmental cue that acts through actomyosin contractility to regulate the invasive properties of GBM tumor cells.
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PMID:The mechanical rigidity of the extracellular matrix regulates the structure, motility, and proliferation of glioma cells. 1943 97


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