P2X7 targeting inhibits growth of human mesothelioma
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Francesca Amoroso1, Erica Salaro1, Simonetta Falzoni1, Paola Chiozzi1, Anna Lisa Giuliani1, Giorgio Cavallesco1, Pio Maniscalco1, Andrea Puozzo1, Ilaria Bononi1, Fernanda Martini1, Mauro Tognon1, Francesco Di Virgilio1
1Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
Francesco Di Virgilio, email: [email protected]
Mauro Tognon, email: [email protected]
Keywords: cancer, mesothelioma, purinergic signalling, extracellular ATP, P2X7
Received: December 16, 2015 Accepted: June 26, 2016 Published: July 06, 2016
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.
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