title: Modulation of metalloproteinase-9 in U87MG glioblastoma cells by A3 adenosine receptors.
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.
authors.affiliation: Department of Clinical and Experimental Medicine, Interdisciplinary Center for the Study of Inflammation, University of Ferrara, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gessi
authors.forename: Valeria
authors.initials: V
authors.lastname: Sacchetto
authors.forename: Eleonora
authors.initials: E
authors.lastname: Fogli
authors.forename: Stefania
authors.initials: S
authors.lastname: Merighi
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Mojgan Aghazadeh
authors.initials: MA
authors.lastname: Tabrizi
authors.forename: Edward
authors.initials: E
authors.lastname: Leung
authors.forename: Stephen
authors.initials: S
authors.lastname: Maclennan
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
mesh_terms: D000241:Adenosine / Q000378:metabolism / Q000502:physiology; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D005909:Glioblastoma / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007295:Inositol Phosphates / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism* / Q000502:physiology; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D043684:Receptor, Adenosine A3 / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology
chemical_list: C435044:1-((1-O-octadecyl-2-O-methylglycero)phospho)-3-deoxy-myo-inositol; D002070:Butadienes; D007093:Imidazoles; D007295:Inositol Phosphates; D009570:Nitriles; D011725:Pyridines; D043684:Receptor, Adenosine A3; D018808:Transcription Factor AP-1; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D000241:Adenosine; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole