title: P2X7 targeting inhibits growth of human mesothelioma.
abstract: Malignant pleural mesothelioma (MPM) is an aggressive tumor refractory to anti-blastic therapy. MPM cells show several genetic and biochemical defects, e.g. overexpression of oncogenes, downregulation of onco-suppressor genes, dysregulation of microRNA, or alteration of intracellular Ca2+ homeostasis and of apoptosis. No information is as yet available on purinergic signalling in this tumor. Signalling via the P2X7 (P2RX7 or P2X7R) purinergic receptor is attracting increasing attention as a pathway involved in cancer cell death or proliferation. In this report we show that the P2X7R is expressed by three MPM cell lines established from MPM patients but not by mesothelial cells from healthy subjects (healthy mesothelial cells, HMCs). MPM cell proliferation was inhibited by in vitro incubation in the presence of selective P2X7R antagonists, as well as by stimulation with the P2X7R agonist BzATP. Systemic administration of the selective P2X7R blocker AZ10606120 inhibited in vivo growth of MPM tumors whether implanted subcutaneously (s.c.) or intraperitoneally (i.p.). Our findings suggest that the P2X7R might be a novel target for the therapy of mesothelioma.
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Amoroso
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Salaro
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Falzoni
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Chiozzi
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Giuliani
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cavallesco
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Pio
authors.initials: P
authors.lastname: Maniscalco
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Puozzo
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bononi
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Martini
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Tognon
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Virgilio
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D001706:Biopsy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008654:Mesothelioma / Q000378:metabolism*; D000086002:Mesothelioma, Malignant; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism; D010997:Pleural Neoplasms / Q000378:metabolism*; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs; D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7
keywords: P2X7; cancer; extracellular ATP; mesothelioma; purinergic signalling