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

Stefania Gessi; Valeria Sacchetto; Eleonora Fogli; Stefania Merighi; Katia Varani; Pier Giovanni Baraldi; Mojgan Aghazadeh Tabrizi; Edward Leung; Stephen Maclennan; Pier Andrea Borea

doi:10.1016/j.bcp.2010.01.009

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

Biochem Pharmacol. 2010 May 15;79(10):1483-95. doi: 10.1016/j.bcp.2010.01.009. Epub 2010 Jan 21.

Authors

Stefania Gessi¹, Valeria Sacchetto, Eleonora Fogli, Stefania Merighi, Katia Varani, Pier Giovanni Baraldi, Mojgan Aghazadeh Tabrizi, Edward Leung, Stephen Maclennan, Pier Andrea Borea

Affiliation

¹ Department of Clinical and Experimental Medicine, Interdisciplinary Center for the Study of Inflammation, University of Ferrara, Italy.

PMID: 20096265
DOI: 10.1016/j.bcp.2010.01.009

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.

MeSH terms

Adenosine / metabolism
Adenosine / physiology
Blotting, Western
Butadienes / pharmacology
Cell Line, Tumor
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
Extracellular Signal-Regulated MAP Kinases / drug effects
Extracellular Signal-Regulated MAP Kinases / physiology
Glioblastoma / enzymology*
Glioblastoma / metabolism
Humans
Imidazoles / pharmacology
Inositol Phosphates / pharmacology
JNK Mitogen-Activated Protein Kinases / drug effects
JNK Mitogen-Activated Protein Kinases / physiology
Matrix Metalloproteinase 9 / metabolism*
Matrix Metalloproteinase 9 / physiology
Neoplasm Invasiveness / physiopathology
Nitriles / pharmacology
Phosphorylation
Pyridines / pharmacology
Receptor, Adenosine A3 / metabolism*
Receptor, Adenosine A3 / physiology
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factor AP-1 / drug effects
Transcription Factor AP-1 / metabolism
Transcription Factor AP-1 / physiology
Transcriptional Activation / drug effects
Transcriptional Activation / physiology

Substances

1-((1-O-octadecyl-2-O-methylglycero)phospho)-3-deoxy-myo-inositol
Butadienes
Imidazoles
Inositol Phosphates
Nitriles
Pyridines
Receptor, Adenosine A3
Transcription Factor AP-1
U 0126
Extracellular Signal-Regulated MAP Kinases
JNK Mitogen-Activated Protein Kinases
Matrix Metalloproteinase 9
Adenosine
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole