scholarly journals GFAP splice variants fine-tune glioma cell invasion and tumour dynamics by modulating migration persistence

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Rebeca Uceda-Castro ◽  
Jessy V. van Asperen ◽  
Claire Vennin ◽  
Jacqueline A. Sluijs ◽  
Emma J. van Bodegraven ◽  
...  
Keyword(s):  
Splice Variants ◽  
Ex Vivo ◽  
Glioma Cells ◽  
Brain Parenchyma ◽  
Intermediate Filament Protein ◽  
Glioma Invasion ◽  
Primary Brain Tumours ◽  
Invasion Model ◽  
Filament Protein ◽  
The Brain

AbstractGlioma is the most common form of malignant primary brain tumours in adults. Their highly invasive nature makes the disease incurable to date, emphasizing the importance of better understanding the mechanisms driving glioma invasion. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is characteristic for astrocyte- and neural stem cell-derived gliomas. Glioma malignancy is associated with changes in GFAP alternative splicing, as the canonical isoform GFAPα is downregulated in higher-grade tumours, leading to increased dominance of the GFAPδ isoform in the network. In this study, we used intravital imaging and an ex vivo brain slice invasion model. We show that the GFAPδ and GFAPα isoforms differentially regulate the tumour dynamics of glioma cells. Depletion of either isoform increases the migratory capacity of glioma cells. Remarkably, GFAPδ-depleted cells migrate randomly through the brain tissue, whereas GFAPα-depleted cells show a directionally persistent invasion into the brain parenchyma. This study shows that distinct compositions of the GFAPnetwork lead to specific migratory dynamics and behaviours of gliomas.

scholarly journals GFAP splice variants fine-tune glioma cell invasion and tumour dynamics by modulating migration persistence.

2021 ◽  
Author(s):  
Jacco van Rheenen ◽  
Elly Hol ◽  
Claire Vennin ◽  
Jessy van Asperen ◽  
Rebeca Uceda-Castro ◽  
...  
Keyword(s):  
Splice Variants ◽  
Ex Vivo ◽  
Glioma Cells ◽  
Brain Parenchyma ◽  
Intermediate Filament Protein ◽  
Glioma Invasion ◽  
Primary Brain Tumours ◽  
Invasion Model ◽  
Filament Protein ◽  
The Brain

Glioma is the most common form of malignant primary brain tumours in adults. Their highly invasive nature makes the disease incurable to date, emphasizing the importance of better understanding the mechanisms driving glioma invasion. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is characteristic for astrocyte- and neural stem cell-derived gliomas. Glioma malignancy is associated with changes in GFAP alternative splicing, as the canonical isoform GFAPα is downregulated in higher-grade tumours, leading to increased dominance of the GFAPδ isoform in the network. In this study, we used intravital imaging and an ex vivo brain slice invasion model. We show that the GFAPδ and GFAPα isoforms differentially regulate the tumour dynamics of glioma cells. Depletion of either isoform increases the migratory capacity of glioma cells. Remarkably, GFAPδ-depleted cells migrate randomly through the brain tissue, whereas GFAPα-depleted cells show a directionally persistent invasion into the brain parenchyma. This study shows that distinct compositions of the GFAP-network lead to specific migratory dynamics and behaviours of gliomas.

Malignant glioma—induced neuronal cell death in an organotypic glioma invasion model

2005 ◽  
Vol 102 (4) ◽  
pp. 738-744 ◽  
Author(s):  
Ilker Y. Eyüpoglu ◽  
Eric Hahnen ◽  
Alexandra Heckel ◽  
Florian A. Siebzehnrübl ◽  
Rolf Buslei ◽  
...  
Keyword(s):  
Cell Death ◽  
Dentate Gyrus ◽  
Receptor Antagonist ◽  
Neuronal Degeneration ◽  
Malignant Gliomas ◽  
Neuronal Cell ◽  
Glioma Cells ◽  
Brain Parenchyma ◽  
Glioma Invasion ◽  
Invasion Model

✓ Rapid growth and diffuse brain infiltration are hallmarks of malignant gliomas. The underlying molecular pathomechanisms of these tumors, however, remain to be determined. The authors present a novel glioma invasion model that allows researchers to monitor consecutively tumor cell proliferation and migration in an organotypic brain environment. Enhanced green fluorescent protein—labeled F98 rat glioma cells were implanted into slice cultures obtained from a rat hippocampus, and tumor growth was microscopically documented up to 20 days in vitro. Invasion along radially oriented migratory streams could be observed 5 days after implantation of rat F98, human U87MG, and mouse GL261 glioma cells, whereas human Be(2)c neuroblastoma cells and mouse HT22 hippocampal neurons failed to invade the brain parenchyma. Following implantation of F98 glioma cells into the entorhinal cortex, cell death was observed within the infiltrated brain parenchyma as well as in the neuroanatomically connected dentate gyrus. Application of the N-methyl-D-aspartate receptor antagonist MK801 to the culture medium significantly reduced neuronal degeneration in the dentate gyrus, whereas the a-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist GYKI 52466 inhibited peritumoral cytotoxicity. This new model allows researchers to address in a systematic manner the molecular pathways of brain invasion as well as specific tumor—host interactions such as necrosis.

scholarly journals Invasion of the Brain by Listeria monocytogenes Is Mediated by InlF and Host Cell Vimentin

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Pallab Ghosh ◽  
Elizabeth M. Halvorsen ◽  
Dustin A. Ammendolia ◽  
Nirit Mor-Vaknin ◽  
Mary X. D. O’Riordan ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Host Cell ◽  
Bacterial Pathogen ◽  
Surface Protein ◽  
Host Cells ◽  
Intermediate Filament Protein ◽  
Life Threatening ◽  
Host Cell Surface ◽  
Filament Protein ◽  
The Brain

ABSTRACTListeria monocytogenesis a facultative intracellular bacterial pathogen that is frequently associated with food-borne infection. Of particular concern is the ability ofL. monocytogenesto breach the blood-brain barrier, leading to life-threatening meningitis and encephalitis. The mechanisms used by bacterial pathogens to infect the brain are not fully understood. Here we show thatL. monocytogenesis able to utilize vimentin for invasion of host cells. Vimentin is a type III intermediate filament protein within the cytosol but is also expressed on the host cell surface. We found thatL. monocytogenesinteraction with surface-localized vimentin promoted bacterial uptake. Furthermore, in the absence of vimentin,L. monocytogenescolonization of the brain was severely compromised in mice. TheL. monocytogenesvirulence factor InlF was found to bind vimentin and was necessary for optimal bacterial colonization of the brain. These studies reveal a novel receptor-ligand interaction that enhances infection of the brain byL. monocytogenesand highlights the importance of surface vimentin in host-pathogen interactions.IMPORTANCEListeria monocytogenesis an intracellular bacterial pathogen that is capable of invading numerous host cells during infection.L. monocytogenescan cross the blood-brain barrier, leading to life-threatening meningitis. Here we show that anL. monocytogenessurface protein, InlF, is necessary for optimal colonization of the brain in mice. Furthermore, in the absence of vimentin, a cytosolic intermediate filament protein that is also present on the surface of brain endothelial cells, colonization of the brain was significantly impaired. We further show that InlF binds vimentin to mediate invasion of host cells. This work identifies InlF as a bacterial surface protein with specific relevance for infection of the brain and underscores the significance of host cell surface vimentin interactions in microbial pathogenesis.

Antibodies to β-Amyloid Decrease the Blood-to-Brain Transfer of β-Amyloid Peptide1

2002 ◽  
Vol 227 (8) ◽  
pp. 609-615 ◽  
Author(s):  
Weihong Pan ◽  
Beka Solomon ◽  
Lawrence M. Maness ◽  
Abba J. Kastin
Keyword(s):  
Ex Vivo ◽  
Amyloid Β ◽  
Brain Perfusion ◽  
Brain Parenchyma ◽  
Amyloid Angiopathy ◽  
Β Amyloid ◽  
Blocking Antibodies ◽  
The Brain

Amyloid-β peptides (Aβ) play an important role in the pathophysiology of dementia of the Alzheimer's type and in amyloid angiopathy. Aβ outside the CNS could contribute to plaque formation in the brain where its entry would involve interactions with the blood-brain barrier (BBB). Effective antibodies to Aβ have been developed in an effort to vaccinate against Alzheimer's disease. These antibodies could interact with Aβ in the peripheral blood, block the passage of Aβ across the BBB, or prevent Aβ deposition within the CNS. To determine whether the blocking antibodies act at the BBB level, we examined the influx of radiolabeled Aβ (125I-Aβ1-40) into the brain after ex-vivo incubation with the antibodies. Antibody mAb3D6 (élan Company) reduced the blood-to-brain influx of Aβ after iv bolus injection. It also significantly decreased the accumulation of Aβ in brain parenchyma. To confirm the in-vivo study and examine the specificity of mAb3D6, in-situ brain perfusion in serum-free buffer was performed after incubation of 125I-Aβ1-40 with another antibody mAbmc1 (DAKO Company). The presence of mAbmc1 also caused significant reduction of the influx of Aβ into the brain after perfusion. Therefore, effective antibodies to Aβ can reduce the influx of Aβ1-40 into the brain.

Subclones of C6 rat glioma cells differing in intermediate filament protein expression

1991 ◽  
Vol 197 (2) ◽  
pp. 200-206 ◽  
Author(s):  
Kerstin Röser ◽  
Wolfgang Bohn ◽  
Günter Giese ◽  
Klaus Mannweiler
Keyword(s):  
Protein Expression ◽  
Intermediate Filament ◽  
Glioma Cells ◽  
Intermediate Filament Protein ◽  
Rat Glioma ◽  
Filament Protein

Traumatically Induced Brain Stem Hemorrhage and the Computerized Tomographic Scan

Neurosurgery ◽  
1979 ◽  
Vol 4 (2) ◽  
pp. 115-124 ◽  
Author(s):  
Paul R. Cooper ◽  
Kenneth Maravilla ◽  
Joel Kirkpatrick ◽  
Sarah F. Moody ◽  
Frederick H. Sklar ◽  
...  
Keyword(s):  
Ct Scan ◽  
Brain Stem ◽  
Thin Section ◽  
Ex Vivo ◽  
Ct Scanning ◽  
Volume Effect ◽  
Brain Parenchyma ◽  
Ct Scanner ◽  
Cross Sectional ◽  
The Brain

Abstract The computerized tomographic (CT) scan has revolutionized the management of cerebral trauma. Nevertheless, visualization of traumatically induced lesions of the brain stem by the CT scanner remains difficult. Seven patients with autopsy or CT evidence of brain stem hemorrhage were identified over a 1-year period. In six of these patients, brain stem hemorrhage could be defined by CT scan. As part of a prospective study of CT changes after head injury, we performed serial CT scans on six of the seven patients. Clinical experience shows that timing is important for identification of these lesions and that inability to visualize brain stem hematomas may occur because of the development of hematomas after CT scanning, evolution of hemorrhagic lesions that makes them isodense with the surrounding brain stem, patient movement, and technical factors such as the partial volume effect. Experimental injection of fresh blood into the pons and midbrain of cadavers shows that lesions as small as 0.1 ml in volume may be visualized by ex vivo thin section CT scanning techniques. However, the character and anatomical configuration of the hemorrhage may be as important in determining CT visualization as is the volume of the hemorrhage. For example, a hematoma displacing the brain parenchyma was visualized, but a similar-sized small hemorrhage that had diffused through the brain stem tissues was not. Although many of the experimentally placed lesions extended over a rostral-caudal length of 15 mm or more in the brain stem, no lesion was seen on more than three thin section scans. This is explained by the presence of lesions that, although extensive in a rostral-caudal direction, had relatively small cross sectional areas available for identification by the CT scanner. The small size of traumatic lesions of the brain stem and their proximity to bony structures at the base of the skull are not insurmountable obstacles to visualization of brain stem hemorrhages. Serial scanning and the application of thin section computed tomography will lead to identification of most of these lesions.

Amiloride-sensitive Na+ channels contribute to regulatory volume increases in human glioma cells

2007 ◽  
Vol 293 (3) ◽  
pp. C1181-C1185 ◽  
Author(s):  
Sandra B. Ross ◽  
Catherine M. Fuller ◽  
James K. Bubien ◽  
Dale J. Benos
Keyword(s):  
Ion Channel ◽  
Potential Role ◽  
Glioma Cells ◽  
Brain Parenchyma ◽  
Volume Increase ◽  
Cation Conductance ◽  
Normal Human ◽  
Hyperosmolar Solutions ◽  
The Brain

Despite intensive research, brain tumors remain among the most difficult type of malignancies to treat, due largely to their diffusely invasive nature and the associated difficulty of adequate surgical resection. To migrate through the brain parenchyma and to proliferate, glioma cells must be capable of significant changes in shape and volume. We have previously reported that glioma cells express an amiloride- and psalmotoxin-sensitive cation conductance that is not found in normal human astrocytes. In the present study, we investigated the potential role of this ion channel to mediate regulatory volume increase in glioma cells. We found that the ability of the cells to volume regulate subsequent to cell shrinkage by hyperosmolar solutions was abolished by both amiloride and psalmotoxin 1. This toxin is thought to be a specific peptide inhibitor of acid-sensing ion channel (ASIC1), a member of the Deg/ENaC superfamily of cation channels. We have previously shown this toxin to be an effective blocker of the glioma cation conductance. Our data suggest that one potential role for this conductance may be to restore cell volume during the cell's progression thorough the cell cycle and while the tumor cell migrates within the interstices of the brain.

GFA AND INTERMEDIATE FILAMENT PROTEIN IN GLIOMA CELLS

1978 ◽  
Vol 37 (5) ◽  
pp. 669 ◽  
Author(s):  
A. Paetau ◽  
I. Virtanen ◽  
P. Kurki ◽  
S. Stenman ◽  
E. Linder ◽  
...  
Keyword(s):  
Intermediate Filament ◽  
Glioma Cells ◽  
Intermediate Filament Protein ◽  
Filament Protein

scholarly journals Predetermined Interplay of the Projected Malignant Transformation Step as Injury Non- Resolution

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Lawrence M Agius
Keyword(s):  
Tumor Cells ◽  
Malignant Transformation ◽  
System Biology ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Brain Parenchyma ◽  
Cell Component ◽  
The Brain

Non-resolution of carcinogenesis is a paramount consideration in the systems of non-immunogenicity of tumor cells in general and as further projected by the infiltrating glioma cell within the brain parenchyma. In such terms, the performance dynamics for further progression are change attributes that bespeak of the systems of overlap and of interactivity of multiple pathways of pro-apoptosis and of anti-apoptosis as projected by mirrored system biology of cell component injury. It is within the single transformation phenomenon step in malignancy emergence that the pro-apoptosis projects the predetermination for non-resolution of cell component injury and as further determined by non-immunogenicity of the infiltrating glioma cells..

scholarly journals Vimentin: a phosphoprotein under hormonal regulation.

1981 ◽  
Vol 90 (3) ◽  
pp. 803-808 ◽  
Author(s):  
E T Browning ◽  
M M Sanders
Keyword(s):  
Molecular Weight ◽  
Hormonal Regulation ◽  
Glioma Cells ◽  
Intermediate Filament Protein ◽  
Nuclear Fraction ◽  
Matrix Structure ◽  
Insoluble Material ◽  
Nonionic Detergent ◽  
Filament Protein ◽  
Type Intermediate

Past studies of norepinephrine-stimulated protein phosphorylation in intact C-6 glioma cells had identified a 58,000 molecular weight, 5.7 isoelectric point protein (58K-5.7) as a cyclic AMP-dependent phosphoprotein and had shown that 58K-5.7 was one of the most abundant proteins of the nuclear fraction. Initial experiments of present studies showed that the 58K-5.7 protein remained with the nuclear ghost, or matrix structure, after removal of chromatin. Based on the size, acidity, abundance, nonsolubilization by nonionic detergent and salt, and solubilization by urea, the hypothesis was advanced that the 58K-5.7 protein was the vimentin-type intermediate filament protein. The hypothesis was tested by two types of immunochemical experiments. Antisera against hamster vimentin reacted selectively with only the 58K-5.7 protein in polyacrylamide gels of urea-solubilized cellular residues (i.e., nonionic detergent and 0.6 M salt-insoluble material) as determined by immunoautoradiography. Antisera against the pure 58K-5.7 protein of C-6 cells bound selectively to a fibrous array of cellular material typical of vimentin filaments as determined by indirect immunofluorescence. It is concluded that the 58K-5.7 protein is vimentin.

Sign in / Sign up

Export Citation Format

Share Document