scholarly journals Effectiveness of porous silicon nanoparticle treatment at inhibiting the migration of a heterogeneous glioma cell population

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Youssef Abdalla ◽  
Meihua Luo ◽  
Ermei Mäkilä ◽  
Bryan W. Day ◽  
Nicolas H. Voelcker ◽  
...  
Keyword(s):  
Cell Migration ◽  
Porous Silicon ◽  
Volume Regulation ◽  
Glioma Cell ◽  
Silicon Nanoparticles ◽  
Expression Patterns ◽  
Glioma Cells ◽  
Migration Inhibition ◽  
Cellular Volume ◽  
In Vitro Investigation

Abstract Background Approximately 80% of brain tumours are gliomas. Despite treatment, patient mortality remains high due to local metastasis and relapse. It has been shown that transferrin-functionalised porous silicon nanoparticles (Tf@pSiNPs) can inhibit the migration of U87 glioma cells. However, the underlying mechanisms and the effect of glioma cell heterogeneity, which is a hallmark of the disease, on the efficacy of Tf@pSiNPs remains to be addressed. Results Here, we observed that Tf@pSiNPs inhibited heterogeneous patient-derived glioma cells’ (WK1) migration across small perforations (3 μm) by approximately 30%. A phenotypical characterisation of the migrated subpopulations revealed that the majority of them were nestin and fibroblast growth factor receptor 1 positive, an indication of their cancer stem cell origin. The treatment did not inhibit cell migration across large perforations (8 μm), nor cytoskeleton formation. This is in agreement with our previous observations that cellular-volume regulation is a mediator of Tf@pSiNPs’ cell migration inhibition. Since aquaporin 9 (AQP9) is closely linked to cellular-volume regulation, and is highly expressed in glioma, the effect of AQP9 expression on WK1 migration was investigated. We showed that WK1 migration is correlated to the differential expression patterns of AQP9. However, AQP9-silencing did not affect WK1 cell migration across perforations, nor the efficacy of cell migration inhibition mediated by Tf@pSiNPs, suggesting that AQP9 is not a mediator of the inhibition. Conclusion This in vitro investigation highlights the unique therapeutic potentials of Tf@pSiNPs against glioma cell migration and indicates further optimisations that are required to maximise its therapeutic efficacies. Graphic Abstract

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.

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.

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.

Correlated overexpression of metadherin and SND1 in glioma cells

2016 ◽  
Vol 397 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Liping Tong ◽  
Chao Wang ◽  
Xuebin Hu ◽  
Bo Pang ◽  
Zhonghui Yang ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Glioma Cell ◽  
Expression Patterns ◽  
Glioma Cells ◽  
Staphylococcal Nuclease ◽  
Primary Brain Tumor ◽  
Interacting Protein ◽  
Nuclease Domain ◽  
Primary Glioma

Abstract Glioma is the most common primary brain tumor with poor prognosis. Effective treatment of glioma remains a big challenge due to complex pathogenic mechanisms. Previous studies have shown that metadherin (MTDH) and its interacting protein staphylococcal nuclease domain containing 1 (SND1) are overexpressed in many solid tumors. To elucidate the role of MDTH and SND1 in the pathogenesis of glioma, we examined the expression of MTDH and SND1 in primary glioma tissues and found that both MTDH and SND1 were highly expressed, with similar expression patterns. Co-expression of MTDH and SND1 was associated with advanced glioma grades. In addition, we detected the interaction between MTDH and SND1 in cultured glioma cell lines. MTDH could promote the expression of p65 and SND1 in glioma cells. However, enhanced SND1 expression by MTDH was abolished by the inhibition of p65. In conclusion, we demonstrated high expression levels MTDH and SND1 in primary glioma tissues. MTDH might promote glioma by inducing SND1 expression through the activation of NF-κB pathway. MTDH and SND1 may serve as the indicator of malignancy and prognosis as well as therapeutic targets for patients with glioma.

scholarly journals Mesenchymal stem cell-derived exosomal microRNA-133b suppresses glioma progression via Wnt/β-catenin signaling pathway by targeting EZH2

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Haiyang Xu ◽  
Guifang Zhao ◽  
Yu Zhang ◽  
Hong Jiang ◽  
Weiyao Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Glioma Cell ◽  
Expression Patterns ◽  
Glioma Cells ◽  
Invasion And Migration ◽  
Glioma Cell Proliferation ◽  
And Migration

Abstract Background Mesenchymal stem cells (MSCs) play a significant role in cancer initiation and metastasis, sometimes by releasing exosomes that mediate cell communication by delivering microRNAs (miRNAs). This study aimed to investigate the effects of exosomal miR-133b derived from MSCs on glioma cell behaviors. Methods Microarray-based analysis identified the differentially expressed genes (DEGs) in glioma. The expression patterns of EZH2 and miR-133b along with interaction between them were clarified in glioma. The expression of miR-133b and EZH2 in glioma cells was altered to examine their functions on cell activities. Furthermore, glioma cells were co-cultured with MSC-derived exosomes treated with miR-133b mimic or inhibitor, and EZH2-over-expressing vectors or shRNA against EZH2 to characterize their effect on proliferation, invasion, and migration of glioma cells in vitro. In vivo assays were also performed to validate the in vitro findings. Results miR-133b was downregulated while EZH2 was upregulated in glioma tissues and cells. miR-133b was found to target and negatively regulate EZH2 expression. Moreover, EZH2 silencing resulted in inhibited glioma cell proliferation, invasion, and migration. Additionally, MSC-derived exosomes containing miR-133b repressed glioma cell proliferation, invasion, and migration by inhibiting EZH2 and the Wnt/β-catenin signaling pathway. Furthermore, in vivo experiments confirmed the tumor-suppressive effects of MSC-derived exosomal miR-133b on glioma development. Conclusion Collectively, the obtained results suggested that MSC-derived exosomes carrying miR-133b could attenuate glioma development via disrupting the Wnt/β-catenin signaling pathway by inhibiting EZH2, which provides a potential treatment biomarker for glioma.

Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells

2020 ◽  
Vol 20 (6) ◽  
pp. 734-750
Author(s):  
Wallax A.S. Ferreira ◽  
Rommel R. Burbano ◽  
Claudia do Ó. Pessoa ◽  
Maria L. Harada ◽  
Bárbara do Nascimento Borges ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Glioma Cell ◽  
Molecular Mechanisms ◽  
Glioma Cells ◽  
Dependent Manner ◽  
M Cell ◽  
Trypan Blue Exclusion ◽  
Cycle Arrest

Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

scholarly journals M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jie Yao ◽  
Zefen Wang ◽  
Yong Cheng ◽  
Chao Ma ◽  
Yahua Zhong ◽  
...  
Keyword(s):  
Cell Migration ◽  
Western Blot ◽  
Signaling Pathway ◽  
Target Gene ◽  
Glioma Cells ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
M2 Macrophage ◽  
Mtor Signaling Pathway ◽  
Cell Migration And Invasion

Abstract Background Glioma, the most common primary brain tumor, account Preparing figures for 30 to 40% of all intracranial tumors. Herein, we aimed to study the effects of M2 macrophage-derived exosomal microRNAs (miRNAs) on glioma cells. Methods First, we identified seven differentially expressed miRNAs in infiltrating macrophages and detected the expression of these seven miRNAs in M2 macrophages. We then selected hsa-miR-15a-5p (miR-15a) and hsa-miR-92a-3p (miR-92a) for follow-up studies, and confirmed that miR-15a and miR-92a were under-expressed in M2 macrophage exosomes. Subsequently, we demonstrated that M2 macrophage-derived exosomes promoted migration and invasion of glioma cells, while exosomal miR-15a and miR-92a had the opposite effects on glioma cells. Next, we performed the target gene prediction in four databases and conducted target gene validation by qRT-PCR, western blot and dual luciferase reporter gene assays. Results The results revealed that miR-15a and miR-92a were bound to CCND1 and RAP1B, respectively. Western blot assays demonstrated that interference with the expression of CCND1 or RAP1B reduced the phosphorylation level of AKT and mTOR, indicating that both CCND1 and RAP1B can activate the PI3K/AKT/mTOR signaling pathway. Conclusion Collectively, these findings indicate that M2 macrophage-derived exosomal miR-15a and miR-92a inhibit cell migration and invasion of glioma cells through PI3K/AKT/mTOR signaling pathway.

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