Possible Future Issues in the Treatment of Glioblastomas: Special Emphasis on Cell Migration and the Resistance of Migrating Glioblastoma Cells to Apoptosis

2005 ◽  
Vol 23 (10) ◽  
pp. 2411-2422 ◽  
Author(s):  
Florence Lefranc ◽  
Jacques Brotchi ◽  
Robert Kiss
Keyword(s):  
Cell Death ◽  
Cell Migration ◽  
Programmed Cell Death ◽  
Signaling Pathways ◽  
Glioma Cell ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
Present Review ◽  
Type I ◽  
Glioma Cell Migration

Purpose The present review aims to emphasize that malignant gliomas are characterized by the diffuse invasion of distant brain tissue by a myriad of single migrating cells that exhibit decreased levels of apoptosis (programmed cell death type I), thus a resistance to cytotoxic insult. Methods The present review surveys the molecular mechanisms of migration in malignant gliomas and potential issues arising from treatments, in addition to relationships between glioma cell migration and resistance to apoptosis in terms of the molecular signaling pathways. Results Clinical and experimental data demonstrate that glioma cell migration is a complex combination of multiple molecular processes, including the alteration of tumor cell adhesion to a modified extracellular matrix, the secretion of proteases by the cells, and modifications to the actin cytoskeleton. Intracellular signaling pathways involved in the acquisition of resistance to apoptosis by migrating glioma cells concern PI3K, Akt, mTOR, NF-κB, and autophagy (programmed cell death type II). Conclusion A number of signaling pathways can be constitutively activated in migrating glioma cells, thus rendering these cells resistant to cytotoxic insults. However, these pathways are not all constitutively activated at the same time in any one glioma. Particular inhibitors should therefore only be chosen if the target is present in the tumor tissue, but this is only possible if individual patients are submitted to the molecular profiling of their tumors before undergoing any treatment to combat their migratory glioma cells. Specific antimigratory compounds should be added to conventional radio- and/or chemotherapy.

scholarly journals A model for glioma cell migration on collagen and astrocytes

2007 ◽  
Vol 5 (18) ◽  
pp. 75-83 ◽  
Author(s):  
M Aubert ◽  
M Badoual ◽  
C Christov ◽  
B Grammaticos
Keyword(s):  
Cell Migration ◽  
Gap Junction ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Migration Patterns ◽  
Gap Junction Communication ◽  
Experimental Findings ◽  
Glioma Cell Migration ◽  
Gap Junction Inhibition

We present a model for the migration of glioma cells on substrates of collagen and astrocytes. The model is based on a cellular automaton where the various dynamical effects are introduced through adequate evolution rules. Using our model, we investigate the role of homotype and heterotype gap junction communication and show that it is possible to reproduce the corresponding experimental migration patterns. In particular, we confirm the experimental findings that inhibition of homotype gap junctions favours migration while heterotype inhibition hinders it. Moreover, the effect of heterotype gap junction inhibition dominates that of homotype inhibition.

Induction of glioma cell migration by vitronectin in human serum and cerebrospinal fluid

2007 ◽  
Vol 107 (3) ◽  
pp. 578-585 ◽  
Author(s):  
Yuji Fukushima ◽  
Masakazu Tamura ◽  
Hidemitsu Nakagawa ◽  
Kazuyuki Itoh
Keyword(s):  
Cerebrospinal Fluid ◽  
Cell Migration ◽  
Healthy Volunteers ◽  
Human Serum ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Heat Inactivation ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Glioma Cell Migration

Object Malignant gliomas are often highly invasive and can migrate along blood vessels. The purpose of the current study was to identify the substance in human serum and/or cerebrospinal fluid (CSF) that promotes glioma cell migration. Methods The authors used a Boyden chamber cell migration assay to study the effect of serum from patients with glioma and healthy volunteers on chemotaxis of A172 human glioma cells. Heat inactivation, trypsinization, and ultra-filtration of serum were used to establish the nature of the active factor. Vitronectin and fibronectin were chosen for further investigations; chemotactic effects were studied in both serum and CSF. Results Serum from both patients with glioma and healthy volunteers was found to promote chemotaxis of human glioma cells. This activity was greatly reduced by heat inactivation or trypsinization. Fractionation of the serum by ultrafiltration through membranes with various pore sizes showed that the active molecule was larger than 50 kD. Antibodies against integrin αv or αvβ5 or arginine-glycine-aspartic acid–containing peptides, both of which block the vitronectin–glioma cell interactions, significantly reduced serum-induced cell migration, whereas blocking the interaction of glioma cells with fibronectin had no effect. Furthermore, the ability of serum to promote the migration of A172 or T98G glioma cells was suppressed by immunodepletion of vitronectin and restored by the addition of exogenous vitronectin. The migration of glioma cells induced by CSF collected from the postoperative cavity of a malignant glioma patient was also reduced by blocking the interaction of glioma cells with vitronectin. Conclusions These results suggest that vitronectin is one of the major factors in serum- and CSF-induced glioma cell migration.

scholarly journals Targeting Aryl Hydrocarbon Receptor with small molecule, 1′H-indole-3′-carbonyl-thiazole-4-carboxylic acid methyl ester blocked human glioma cell invasion via MYH9

2020 ◽  
Author(s):  
Lijiao Zhao ◽  
Qiuting Shu ◽  
Hui Sun ◽  
Yunlong Ma ◽  
Dandan Kang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Carboxylic Acid ◽  
Methyl Ester ◽  
Glioma Cell ◽  
Acid Methyl Ester ◽  
Glioma Cells ◽  
Human Glioma ◽  
Aryl Hydrocarbon ◽  
Acid Methyl ◽  
Glioma Cell Migration

AbstractAryl hydrocarbon receptor (AHR) was a master regulator of anti-tumor cell migration in various cell types. Whether and how AHR regulates glioma cell migration is largely unknown. We found that small molecule 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous AHR ligand, can significantly block glioma cell migration and invasion in vitro, ex vivo and in vivo. Knocking down AHR by siRNA abolished ITE’s migration-inhibiting effects. ITE increased the number of filopodia-like protrusion formation, but reduced protrusion attachment to the extracellular matrix, and inhibited the rear retraction of migrating glioma cells. Moreover, both mesenchymal and amoeboid migrating cells were observed in the DMSO control group while none of the cells display amoeboid migration in the ITE treated group. MYH9 was significantly reduced by ITE treatment in human glioma cells. Over-expression of MYH9 abrogated ITE’s migration-inhibiting effects, with the expression level of MYH9 correlated with cell migration ability. Since MYH9 is a component of non-muscle myosin IIA (NMIIA), which is essential for cell migration in 3D confined space, and not a discovered target of AHR, the fact that ITE affects MYH9 via AHR opens a new research and development avenue.

scholarly journals Autophagy, the Trojan horse to combat glioblastomas

2006 ◽  
Vol 20 (4) ◽  
pp. E7 ◽  
Author(s):  
Florence Lefranc ◽  
Robert Kiss
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Intracellular Signaling ◽  
Malignant Gliomas ◽  
Mammalian Target Of Rapamycin ◽  
Brain Parenchyma ◽  
Trojan Horse ◽  
Type I ◽  
Phosphatidylinositol 3 Kinase ◽  
Diffuse Infiltration

✓ Malignant gliomas, among which glioblastomas constitute the largest group, are characterized by a dramatically diffuse infiltration into the brain parenchyma with, as a consequence, the fact that no patient with glioblastoma multiforme (GBM) has been cured to date. Migrating GBM cells are resistant to apoptosis (Type I programmed cell death), and thus to radiotherapy and conventional chemotherapy, because of the constitutive activation of several intracellular signaling pathways, of which the most important identified to date are the pathways controlled by phosphatidylinositol 3-kinase, Akt, and the mammalian target of rapamycin (mTOR). Migrating GBM cells seem to be less prone to resist autophagy (Type II programmed cell death), and disruption of the pathway controlled by mTOR induces marked autophagic processes in GBM cells. Temozolomide is the most efficacious cytotoxic drug employed today to combat glioblastoma, and this drug exerts its cytotoxic activity through proautophagic processes. Thus, autophagy represents a kind of Trojan horse that can be used to bypass, at least partly, the dramatic resistance of glioblastoma to radiotherapy and proapoptotic-related chemotherapy.

Glioma cell migration and invasion as potential target for novel treatment strategies

2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Ulrike Naumann ◽  
Patrick Harter ◽  
Jennifer Rubel ◽  
Elena Ilina ◽  
Anna-Eva Blank ◽  
...  
Keyword(s):  
Cell Migration ◽  
Glioma Cell ◽  
Treatment Strategies ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Perivascular Spaces ◽  
Existing Structures ◽  
Preclinical Treatment ◽  
The Brain ◽  
Glioma Cell Migration

AbstractDiffuse human gliomas constitute a group of most treatment-refractory tumors even if maximum treatment strategies including neurosurgical resection followed by combined radio-/chemotherapy are applied. In contrast to most other neoplasms, diffusely infiltrating gliomas invade the brain along pre-existing structures such as axonal tracts and perivascular spaces. Even in cases of early diagnosis single or small clusters of glioma cells are already encountered far away from the main tumor bulk. Complex interactions between glioma cells and the surrounding extracellular matrix and considerable changes in the cytoskeletal apparatus are prerequisites for the cellular movement of glioma cells through the brain thereby escaping from most current treatments. This review provides an overview about classical and current concepts of glioma cell migration/invasion and promising preclinical treatment approaches.

S1P2 receptors mediate inhibition of glioma cell migration through Rho signaling pathways independent of PTEN

2008 ◽  
Vol 366 (4) ◽  
pp. 963-968 ◽  
Author(s):  
Enkhzol Malchinkhuu ◽  
Koichi Sato ◽  
Tomohiko Maehama ◽  
Chihiro Mogi ◽  
Hideaki Tomura ◽  
...  
Keyword(s):  
Cell Migration ◽  
Signaling Pathways ◽  
Glioma Cell ◽  
Glioma Cell Migration

PSMB8 regulates glioma cell migration, proliferation, and apoptosis through modulating ERK1/2 and PI3K/AKT signaling pathways

2018 ◽  
Vol 100 ◽  
pp. 205-212 ◽  
Author(s):  
Bing-ya Yang ◽  
Jing-wei Song ◽  
Hong-zhi Sun ◽  
Ji-cheng Xing ◽  
Zhi-hui Yang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Signaling Pathways ◽  
Glioma Cell ◽  
Akt Signaling ◽  
Proliferation And Apoptosis ◽  
Glioma Cell Migration

Glial cytotoxicity of low doses of cadmium as a model of heavy metal pollution influence on vertebrates

2020 ◽  
Vol 31 (1) ◽  
pp. 3-10
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
A. M. Hahut ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Oxidative Damage ◽  
Cadmium Chloride ◽  
Glioma Cells ◽  
Low Doses ◽  
Genotoxic Effects ◽  
Cadmium Ions

Cadmium is a common transition metal that entails an extremely wide range of toxic effects in humans and animals. The cytotoxicity of cadmium ions and its compounds is due to various genotoxic effects, including both DNA damage and chromosomal aberrations. Some bone diseases, kidney and digestive system diseases are determined as pathologies that are closely associated with cadmium intoxication. In addition, cadmium is included in the list of carcinogens because of its ability to initiate the development of tumors of several forms of cancer under conditions of chronic or acute intoxication. Despite many studies of the effects of cadmium in animal models and cohorts of patients, in which cadmium effects has occurred, its molecular mechanisms of action are not fully understood. The genotoxic effects of cadmium and the induction of programmed cell death have attracted the attention of researchers in the last decade. In recent years, the results obtained for in vivo and in vitro experimental models have shown extremely high cytotoxicity of sublethal concentrations of cadmium and its compounds in various tissues. One of the most studied causes of cadmium cytotoxicity is the development of oxidative stress and associated oxidative damage to macromolecules of lipids, proteins and nucleic acids. Brain cells are most sensitive to oxidative damage and can be a critical target of cadmium cytotoxicity. Thus, oxidative damage caused by cadmium can initiate genotoxicity, programmed cell death and inhibit their viability in the human and animal brains. To test our hypothesis, cadmium cytotoxicity was assessed in vivo in U251 glioma cells through viability determinants and markers of oxidative stress and apoptosis. The result of the cell viability analysis showed the dose-dependent action of cadmium chloride in glioma cells, as well as the generation of oxidative stress (p <0.05). Calculated for 48 hours of exposure, the LD50 was 3.1 μg×ml-1. The rates of apoptotic death of glioma cells also progressively increased depending on the dose of cadmium ions. A high correlation between cadmium concentration and apoptotic response (p <0.01) was found for cells exposed to 3–4 μg×ml-1 cadmium chloride. Moreover, a significant correlation was found between oxidative stress (lipid peroxidation) and induction of apoptosis. The results indicate a strong relationship between the generation of oxidative damage by macromolecules and the initiation of programmed cell death in glial cells under conditions of low doses of cadmium chloride. The presented results show that cadmium ions can induce oxidative damage in brain cells and inhibit their viability through the induction of programmed death. Such effects of cadmium intoxication can be considered as a model of the impact of heavy metal pollution on vertebrates.

Sign in / Sign up

Export Citation Format

Share Document