scholarly journals Guanylate binding protein 1 is a novel effector of EGFR-driven invasion in glioblastoma

2011 ◽  
Vol 208 (13) ◽  
pp. 2657-2673 ◽  
Author(s):  
Ming Li ◽  
Akitake Mukasa ◽  
Maria del-Mar Inda ◽  
Jianhua Zhang ◽  
Lynda Chin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cell Invasion ◽  
Glioma Cell ◽  
Binding Protein ◽  
Brain Parenchyma ◽  
Normal Brain ◽  
Matrix Metalloproteinase 1 ◽  
Egfr Expression ◽  
Egfr Activation ◽  
Guanylate Binding Protein

Although GBP1 (guanylate binding protein 1) was among the first interferon-inducible proteins identified, its function is still largely unknown. Epidermal growth factor receptor (EGFR) activation by amplification or mutation is one of the most frequent genetic lesions in a variety of human tumors. These include glioblastoma multiforme (GBM), which is characterized by independent but interrelated features of extensive invasion into normal brain parenchyma, rapid growth, necrosis, and angiogenesis. In this study, we show that EGFR activation promoted GBP1 expression in GBM cell lines through a signaling pathway involving Src and p38 mitogen-activated protein kinase. Moreover, we identified YY1 (Yin Yang 1) as the downstream transcriptional regulator regulating EGFR-driven GBP1 expression. GBP1 was required for EGFR-mediated MMP1 (matrix metalloproteinase 1) expression and glioma cell invasion in vitro. Although deregulation of GBP1 expression did not affect glioma cell proliferation, overexpression of GBP1 enhanced glioma cell invasion through MMP1 induction, which required its C-terminal helical domain and was independent of its GTPase activity. Reducing GBP1 levels by RNA interference in invasive GBM cells also markedly inhibited their ability to infiltrate the brain parenchyma of mice. GBP1 expression was high and positively correlated with EGFR expression in human GBM tumors and cell lines, particularly those of the neural subtype. Together, these findings establish GBP1 as a previously unknown link between EGFR activity and MMP1 expression and nominate it as a novel potential therapeutic target for inhibiting GBM invasion.

Identification of Guanylate-Binding Protein 1 as a Potential Oral Cancer Marker Involved in Cell Invasion Using Omics-Based Analysis

2011 ◽  
Vol 10 (8) ◽  
pp. 3778-3788 ◽  
Author(s):  
Chia-Jung Yu ◽  
Kai-Ping Chang ◽  
Yin-Ju Chang ◽  
Chia-Wei Hsu ◽  
Ying Liang ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cell Invasion ◽  
Binding Protein ◽  
Cancer Marker ◽  
Guanylate Binding Protein

scholarly journals CBMT-18. THE ROLE OF BIOMARKER CANDIDATE GELSOLIN AND ITS MICRORNAS IN GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi36-vi37
Author(s):  
Mitsutoshi Nakada ◽  
Jiakang Zhang ◽  
Taskuya Furuta ◽  
Shabierjiang Jiapaer ◽  
Sho Tamai ◽  
...  
Keyword(s):  
Cell Lines ◽  
Glioma Cell ◽  
Glycogen Synthase ◽  
Inverse Correlation ◽  
Progression Free Survival ◽  
Expression Level ◽  
Normal Brain ◽  
Kaplan Meier ◽  
Glioma Cell Lines ◽  
Proliferation And Invasion

Abstract BACKGROUND Among potential glioblastoma (GBM) blood biomarkers that we identified recently, we focused on gelsolin (GSN), a key regulator of actin filament disassembly. GSN was significantly lower in the blood of patients with GBM than in that of healthy controls. In this study, we analyzed the function of GSN and identified microRNAs (miRs) involved in GSN expression in GBM. METHODS QRT-PCR and western blot were introduced to evaluate the expression level of GSN in normal brain and GBM tissue. The localization of GSN was examined by immunohistochemistry and immunocytochemistry using human samples. The association between the expression level of GSN and progression free survival (PFS) /overall survival (OS) in GBM was assessed by Kaplan-Meier analysis. The function of GSN and its signal transduction in glioma cell lines were analyzed using small interfering RNA (siRNA) knockdown of GSN. Additionally, miRs controlling GSN expression were retrieved from databases of miRs, and miRs related to GSN expression were identified in GBM tissues. RESULTS The expression level of GSN was significantly lower in GBM tissues compared to normal brains. Normal astrocytes mainly expressed GSN. High expressor of GSN showed longer PFS and OS than low expressor. Proliferation and invasion in glioma cell lines were significantly promoted by siRNA for GSN accompanied with the activation of glycogen synthase kinase 3β. In GBM tissues, the expression levels of GSN and miR-654-5p, 450b-5p showed an inverse correlation. The inhibitor for miR-654-5p and miR-450b-5p accelerated GSN expression resulting reduction of proliferation. CONCLUSION GSN plays a role as suppressor of proliferation and invasion in GBM. miR-654-5p and miR-450b-5p which control GSN expression can be targets against GBM.

scholarly journals Overexpression of RKIP Inhibits Cell Invasion in Glioma Cell Lines through Upregulation of miR-98

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Zigui Chen ◽  
Quan Cheng ◽  
Zhiming Ma ◽  
Haipeng Xi ◽  
Renjun Peng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Invasion ◽  
Tumor Invasion ◽  
Glioma Cell ◽  
Target Gene ◽  
Kinase Inhibitor ◽  
Vital Role ◽  
Metastasis Suppressor ◽  
Normal Brain ◽  
Glioma Cell Proliferation

Raf-1 kinase inhibitor protein (RKIP) is a tumor and metastasis suppressor in cancer cells. MicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on antimetastasis strategy. In this study, we found that the expression of RKIP and miR-98 in glioma tissues were significantly lower than that in normal brain tissues. Overexpression of RKIP upregulated miR-98 expression and inhibited glioma cell invasion and miR-98 target gene HMGA2 but had no effect in glioma cell proliferation. Moreover, forced expression of miR-98 accelerated the inhibition of glioma cell invasion and the expression of HMGA2 also had no effect in glioma cell proliferation. Our findings newly described RKIP/miR-98 to HMGA2 link and provided a potential mechanism for glioma cell invasion. RKIP and miR-98 may illustrate the potential therapeutic utility of signaling pathway signatures.

Inhibition of cell invasion by indomethacin on glioma cell lines: in vitro study

2005 ◽  
Vol 72 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Maode Wang ◽  
Daizo Yoshida ◽  
Shouxun Liu ◽  
Akira Teramoto
Keyword(s):  
Cell Lines ◽  
Cell Invasion ◽  
Glioma Cell ◽  
In Vitro Study ◽  
Vitro Study ◽  
Glioma Cell Lines

Molecular determinants of glioma cell migration and invasion

2001 ◽  
Vol 94 (6) ◽  
pp. 978-984 ◽  
Author(s):  
Christine Wild-Bode ◽  
Michael Weller ◽  
Wolfgang Wick
Keyword(s):  
Cell Lines ◽  
Cell Invasion ◽  
Glioma Cell ◽  
Growth Patterns ◽  
Migration And Invasion ◽  
Integrin Expression ◽  
Content Type ◽  
Expression Levels ◽  
Glioma Cell Lines ◽  
Fine Print

Object. Migration and invasion are important prerequisites for the infiltrative and destructive growth patterns of malignant gliomas. Infiltrative growth prevents complete tumor resection and causes significant neurological morbidity and mortality. Methods. The authors assessed the expression of matrix metalloproteinases (MMPs) at messenger RNA and protein levels, MMP-2 and MMP-9 activities, and expression levels of a panel of anti- and proapoptotic proteins of the BCL-2 family. They then correlated their findings with αVβ3 integrin expression and the migratory and invasive potentials in 12 human malignant glioma cell lines. Multiple MMPs were expressed by most cell lines. The levels of MMP-2 and MMP-3 and the activities of MMP-2 and MMP-9 correlated with tumor cell invasion. Migration and invasion were also correlated. Although the expression levels of αVβ3 integrin did not predict migration or invasion, a neutralizing αVβ3 integrin antibody inhibited migration and invasion selectively in cell lines that contained a high level of αVβ3 integrin expression, thus indicating the important role of αVβ3 integrin for migration and invasion in this subset of cell lines. An expression pattern of BCL-2 family proteins that favor resistance to apoptosis was associated with enhanced migration, invasion, and MMP activity. Wild-type p53 cell lines migrated farther than mutant p53 cell lines. Conclusions. Activities of MMP-2 and MMP-9 are the best predictors of glioma cell invasion. The αVβ3 integrin mediates migration and invasion in a subset of glioma cell lines, but these processes do not depend on αVβ3 integrin expression. Antiapoptotic BCL-2 family protein expression is a predictor of efficient migration and invasion.

scholarly journals Downregulation of uPA, uPAR and MMP-9 using small, interfering, hairpin RNA (siRNA) inhibits glioma cell invasion, angiogenesis and tumor growth

2004 ◽  
Vol 1 (2) ◽  
pp. 165-176 ◽  
Author(s):  
CHRISTOPHER S. GONDI ◽  
SAJANI S. LAKKA ◽  
DZUNG H. DINH ◽  
WILLIAM C. OLIVERO ◽  
MEENA GUJRATI ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Gene Silencing ◽  
Cell Invasion ◽  
Glioma Cell ◽  
Immunohistochemical Analysis ◽  
Normal Brain ◽  
Invasion Assay ◽  
Hairpin Rna ◽  
Protein Levels ◽  
Extracellular Matrix Components

The diffuse, extensive infiltration of malignant gliomas into the surrounding normal brain is believed to rely on modification of the proteolysis of extracellular matrix components. Our previous results clearly demonstrate that uPA, uPAR and MMP-9 concentrations increase significantly during tumor progression and that tumor growth can be inhibited with antisense stable clones of these molecules. Because antisense-mediated gene silencing does not completely inhibit the translation of target mRNA and high concentrations of antisense molecules are required to achieve gene silencing, we used the RNAi approach to silence uPA, uPAR and MMP-9 in this study. We examined a cytomegalovirus (CMV) promoter-driven DNA-template approach to induce hairpin RNA (hpRNA)-triggered RNAi to inhibit uPA, uPAR and MMP-9 gene expression with a single construct. uPAR protein levels and enzymatic activity of uPA and MMP-9 were found to significantly decrease in cells transfected with a plasmid expressing hairpin siRNA for uPAR, uPA and MMP-9. pU2M-transfected SNB19 cells significantly decreased uPA, uPAR and MMP-9 expression compared to mock and EV/SV-transfected cells, determined by immunohistochemical analysis. Furthermore, the effect of the single constructs for these molecules was a specific inhibition of their respective protein levels, as demonstrated by immunohistochemical analysis. After transfection with a plasmid vector expressing dsRNA for uPA, uPAR and MMP-9, glioma-cell invasion was retarded compared with mock and EV/SV-treated groups, demonstrated by Matrigel-invasion assay and spheroid-invasion assay. Downregulation of uPA, uPAR and MMP-9 using RNAi inhibited angiogenesis in an in vitro (co-culture) model. Direct intratumoral injections of plasmid DNA expressing hpRNA for uPA, uPAR and MMP-9 significantly regressed pre-established intracranial tumors in nude mice. In addition, cells treated with RNAi for uPAR, uPA and MMP-9 showed reduced pERK levels compared with parental and EV/SV-treated SNB19 cells. Our results support the therapeutic potential of RNAi as a method for gene therapy in treating gliomas.

scholarly journals Overexpression of DcR3 and Its Significance on Tumor Cell Differentiation and Proliferation in Glioma

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Suning Huang ◽  
Gang Chen ◽  
Yiwu Dang ◽  
Long-Hua Chen
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Normal Brain ◽  
Ki 67 ◽  
Glioma Cell Lines ◽  
Positive Correlations ◽  
Differentiation And Proliferation ◽  
Tumor Cell Differentiation

Background.Overexpression of decoy receptor 3 (DcR3) have been reported in various classes of malignancies. However, its expression and clinicopathological contribution in gliomas has not been fully elucidated.Objective.To explore the expression and clinical significance of DcR3 protein in relation to tumor cell differentiation and proliferation in glioma cell lines and tissues.Methods.One hundred and twenty-five samples of glioma patients and 18 cases of normal brain tissues were recruited. The expression of DcR3 protein was detected using immunohistochemistry. Tumor differentiation was assessed by histologic characters and the status of glial fibrillary acidic protein (GFAP). Tumor cell labeling indexes (LIs) of Ki-67 and PCNA were also obtained. The relationship between the DcR3 level and clinicopathological features was investigated, including tumor differentiation, LIs, and survival. Meanwhile, the expression of DcR3 protein was also measured in the supernatants of 8 glioma cell lines and glioma cells freshly prepared from 8 human glioblastoma specimens by using western blot.Results.The level of DcR3 protein in gliomas was significantly higher than that in normal brain tissues (P<0.01). DcR3 expression showed positive correlations with tumor pathological grade(r=0.621,P<0.01)and negative with GFAP expression (r=-0.489,P<0.01). Furthermore, there were positive correlations between DcR3 expression and Ki-67, PCNA LIs (r=0.529,P<0.01;r=0.556,P<0.01). The survival in the DcR3 negative group was 50 ± 1.79 months, longer than that of the DcR3 positive group (48.36 ± 2.90), however, without significance(P=0.149). Different levels of DcR3 could also be detected in the culturing supernatants of all the 8 glioma cell lines and glioma cells freshly obtained from 8 human glioblastoma specimens.Conclusions.The overexpression of DcR3 might play a crucial role in the tumorigenesis, differentiation, and proliferation of glioma.

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