Gene expression profiling of the anti-glioma effect of Cilengitide

被引:11
作者
Onishi, Manabu [1 ]
Kurozumi, Kazuhiko [1 ]
Ichikawa, Tomotsugu [1 ]
Michiue, Hiroyuki [2 ]
Fujii, Kentaro [1 ]
Ishida, Joji [1 ]
Shimazu, Yosuke [1 ]
Chiocca, E. Antonio [3 ]
Kaur, Balveen [4 ]
Date, Isao [1 ]
机构
[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg, Kita Ku, Okayama 7008558, Japan
[2] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Physiol, Okayama 7008558, Japan
[3] Brigham & Womens Hosp, Neurosurg, Boston, MA 02115 USA
[4] Ohio State Univ, Dardinger Lab Neurooncol & Neurosci, Dept Neurol Surg, Columbus, OH 43210 USA
来源
SPRINGERPLUS | 2013年 / 2卷
关键词
Glioma; Integrin; Cilengitide; Gene expression profiling; Apoptosis; ASPARTIC ACID PEPTIDE; INTEGRIN ALPHA(V)BETA(3); GLIOMA-CELLS; FAS LIGAND; APOPTOSIS; GLIOBLASTOMA; ATTACHMENT; EFFICACY; THERAPY; GROWTH;
D O I
10.1186/2193-1801-2-160
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cilengitide (EMD121974), an inhibitor of the adhesive function of integrins, demonstrated preclinical efficacy against malignant glioma. It is speculated that cilengitide can inhibit tumor growth, invasion, and angiogenesis. However, the effects of cilengitide on these processes have not been sufficiently examined. In this study, we investigated the anti-glioma effect of cilengitide using DNA microarray analysis. U87 Delta EGFR cells (human malignant glioma cell line) were used for this experiment. The cells were harvested after 16 h of cilengitide treatment, and mRNA was extracted. Gene expression and pathway analyses were performed using a DNA microarray (CodeLink (TM) Human Whole Genome Bioarray). The expression of 265 genes was changed with cilengitide treatment. The expression of 214 genes was up-regulated by more than 4-fold and the expression of 51 genes was down-regulated by more than 4-fold compared to the controls. In pathway analysis, "apoptotic cleavage of cellular proteins" and "TNF receptor signaling pathway" were over-represented. Apoptotic-associated genes such as caspase 8 were up-regulated. Gene expression profiling revealed more detailed mechanism of the anti-glioma effect of cilengitide. Genes associated with apoptosis were over-represented following cilengitide treatment.
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页数:11
相关论文
共 43 条
[1]   Inhibition of αvβ3 integrin survival signaling enhances antiangiogenic and antitumor effects of radiotherapy [J].
Abdollahi, A ;
Griggs, DW ;
Zieher, H ;
Roth, A ;
Lipson, KE ;
Saffrich, R ;
Gröne, HJ ;
Hallahan, DE ;
Reisfeld, RA ;
Debus, J ;
Niethammerl, AG ;
Huber, PE .
CLINICAL CANCER RESEARCH, 2005, 11 (17) :6270-6279
[2]   Integrin αVβ3 antagonist Cilengitide enhances efficacy of radiotherapy in endothelial cell and non-small-cell lung cancer models [J].
Albert, Jeffrey M. ;
Cao, Carolyn ;
Ling Geng ;
Leavitt, Lauren ;
Hallahan, Dennis E. ;
Bo Lu .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2006, 65 (05) :1536-1543
[3]   The Integrin Antagonist Cilengitide Activates αVβ3, Disrupts VE-Cadherin Localization at Cell Junctions and Enhances Permeability in Endothelial Cells [J].
Alghisi, Gian Carlo ;
Ponsonnet, Lionel ;
Rueegg, Curzio .
PLOS ONE, 2009, 4 (02)
[4]   Human ICE/CED-3 protease nomenclature [J].
Alnemri, ES ;
Livingston, DJ ;
Nicholson, DW ;
Salvesen, G ;
Thornberry, NA ;
Wong, WW ;
Yuan, JY .
CELL, 1996, 87 (02) :171-171
[5]   Matrix attachment regulates Fas-induced apoptosis in endothelial cells: A role for c-Flip and implications for anoikis [J].
Aoudjit, F ;
Vuori, K .
JOURNAL OF CELL BIOLOGY, 2001, 152 (03) :633-643
[6]   REQUIREMENT OF VASCULAR INTEGRIN ALPHA(V)BETA(3) FOR ANGIOGENESIS [J].
BROOKS, PC ;
CLARK, RAF ;
CHERESH, DA .
SCIENCE, 1994, 264 (5158) :569-571
[7]   INTEGRIN ALPHA(V)BETA(3) ANTAGONISTS PROMOTE TUMOR-REGRESSION BY INDUCING APOPTOSIS OF ANGIOGENIC BLOOD-VESSELS [J].
BROOKS, PC ;
MONTGOMERY, AMP ;
ROSENFELD, M ;
REISFELD, RA ;
HU, TH ;
KLIER, G ;
CHERESH, DA .
CELL, 1994, 79 (07) :1157-1164
[8]  
Burke PA, 2002, CANCER RES, V62, P4263
[9]   Human malignant glioma therapy using anti-αvβ3 integrin agents [J].
Chatterjee, S ;
Matsumura, A ;
Schradermeier, J ;
Gillespie, GY .
JOURNAL OF NEURO-ONCOLOGY, 2000, 46 (02) :135-144
[10]   DEFINITION OF 2 ANGIOGENIC PATHWAYS BY DISTINCT ALPHA(V) INTEGRINS [J].
FRIEDLANDER, M ;
BROOKS, PC ;
SHAFFER, RW ;
KINCAID, CM ;
VARNER, JA ;
CHERESH, DA .
SCIENCE, 1995, 270 (5241) :1500-1502