Modulation of metalloproteinase-9 in U87MG glioblastoma cells by A3 adenosine receptors |
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Authors: | Stefania Gessi Eleonora Fogli Katia Varani Mojgan Aghazadeh Tabrizi Stephen Maclennan |
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Affiliation: | a Department of Clinical and Experimental Medicine, Pharmacology Unit and Interdisciplinary Center for the Study of Inflammation, University of Ferrara, Via Fossato di Mortara 17-19, Ferrara 44100, Italy b Departments of Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara 17-19, Ferrara 44100, Italy c King Pharmaceuticals Research and Development, Inc., Cary, NC, USA |
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Abstract: | 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 A3 receptors activation. We revealed that A3 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). A3 receptor activation stimulated also an increase of extracellular MMP-9 in the supernatants from U87MG glioblastoma cells. Finally, the Matrigel invasion assay demonstrated that A3 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 A3 receptors activation, modulates MMP-9 protein levels and plays a role in increasing invasion of U87MG cells. |
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Keywords: | ADA, adenosine deaminase Ado, adenosine AP-1, activator protein 1 Akt/PKB, protein kinase B CGS 21680, 2-[p-(carboxyethyl)-phenethylamino]-NECA CHA, N6-cyclohexyladenosine Cl-IB-MECA, N6(3-iodobenzyl)2-chloroadenosine-5&prime N-methyluronamide DPA23, 1-deoxy-1-[6-{4-[(phenylcarbamoyl)-methoxy]phenylamino}-9H-purin-9-yl]-N-ethyl-β-d-ribofuranuronamide DPCPX, 1,3-dipropyl-8-cyclopentyl-xanthine EHNA, erythro-9-(2-hydroxy-3-nonyl)adenine ERK1/2, extracellular signal-regulated kinases MMP-9, metalloproteinase-9 MRE 2029F20, N-benzo[1,3]dioxol-5-yl-2-[5-(1,3-dipropyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-1-methyl-1H-pyrazol-3-yl-oxy]-acetamide] MRE 3008F20, 5-N-(4-methoxyphenylcarbamoyl)-amino-8-propyl-2-(2-furyl)-pyrazolo[4,3e]-1,2,4-triazolo[1,5c]pyrimidine NDGA, Nordihydroguaiaretic acid pJNK/SAPK, c-Jun N-terminal kinase/stress-activated protein kinase SB202190, 4-[4-(4-Fluorophenyl)-5-(4-pyridinyl)-1H-imidazol-2-yl]pieno SCH 58261, 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]-pyrimidine SH-5, [d-3-deoxy-2-O-methyl-myo-inositol-1-[(R)-2-methoxy-3-(octadecyloxy)propyl hydrogen phosphate]] siRNA, small interfering RNA SP600125, anthra[1-9cd]pyrazol-6(2H)-one ZM, 241385 (4-(2-[7-amino-2-(2-furyl)-[1,2,4]triazolo-[2,32][1,3,6]triazinyl-amino]ethyl)-phenol) U0126, 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene |
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