Modulation of metalloproteinase-9 in U87MG glioblastoma cells by A3 adenosine receptors

被引:64
作者
Gessi, Stefania [1 ,2 ]
Sacchetto, Valeria [1 ,2 ]
Fogli, Eleonora [1 ,2 ]
Merighi, Stefania [1 ,2 ]
Varani, Katia [1 ,2 ]
Baraldi, Pier Giovanni [3 ]
Tabrizi, Mojgan Aghazadeh [3 ]
Leung, Edward [4 ]
Maclennan, Stephen [4 ]
Borea, Pier Andrea [1 ,2 ]
机构
[1] Univ Ferrara, Chair Pharmacol, Fac Med, Dept Clin & Expt Med,Pharmacol Unit, I-44100 Ferrara, Italy
[2] Univ Ferrara, Interdisciplinary Ctr Study Inflammat, I-44100 Ferrara, Italy
[3] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy
[4] King Pharmaceut Res & Dev Inc, Cary, NC USA
关键词
A(3) adenosine receptors; MMP-9; Glioblastoma cells; Intracellular signalling; Cell invasion; ENDOTHELIAL GROWTH-FACTOR; MATRIX METALLOPROTEINASES; SIGNALING PATHWAYS; MATRIX-METALLOPROTEINASE-9; SECRETION; BIOCHEMICAL-CHARACTERIZATION; TISSUE INHIBITOR; GENE-EXPRESSION; UP-REGULATION; GELATINASE-B; KAPPA-B;
D O I
10.1016/j.bcp.2010.01.009
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In this work, we investigated the biological functions of adenosine (ado) in metalloproteinase-9 (MMP-9) regulation in U87MG human glioblastoma cells The nucleoside was able to increase both MMP-9 mRNA and protein levels through A(3) receptors activation We revealed that A(3) receptor stimulation induced an increase of MMP-9 protein levels in cellular extracts of U87MG cells by phosphorylation of extracellular signal-regulated protein kinases (ERK1/2), c-Jun N-terminal kinase/stress-activated protein kinase (pJNK/SAPK), protein kinase B (Akt/PKB) and finally activator protein 1 (AP-1) A(3) receptor activation stimulated also an increase of extracellular MMP-9 in the supernatants from U87MG glioblastoma cells Finally, the Matrigel invasion assay demonstrated that A(3) receptors, by inducing an increase in MMP-9 levels, was responsible for an increase of glioblastoma cells invasion Collectively, these results suggest that ado, through A(3) receptors activation, modulates MMP-9 protein levels and plays a role in increasing invasion of U87MG cells. (C) 2010 Elsevier Inc All rights reserved.
引用
收藏
页码:1483 / 1495
页数:13
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