PMID- 27391069 OWN - NLM STAT- MEDLINE DCOM- 20180223 LR - 20201218 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 31 DP - 2016 Aug 2 TI - P2X7 targeting inhibits growth of human mesothelioma. PG - 49664-49676 LID - 10.18632/oncotarget.10430 [doi] AB - 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. FAU - Amoroso, Francesca AU - Amoroso F AD - Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. FAU - Salaro, Erica AU - Salaro E AD - Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. FAU - Falzoni, Simonetta AU - Falzoni S AD - Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. FAU - Chiozzi, Paola AU - Chiozzi P AD - Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. FAU - Giuliani, Anna Lisa AU - Giuliani AL AD - Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. FAU - Cavallesco, Giorgio AU - Cavallesco G AD - Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. FAU - Maniscalco, Pio AU - Maniscalco P AD - Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. FAU - Puozzo, Andrea AU - Puozzo A AD - Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. FAU - Bononi, Ilaria AU - Bononi I AD - Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. FAU - Martini, Fernanda AU - Martini F AD - Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. FAU - Tognon, Mauro AU - Tognon M AD - Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. FAU - Di Virgilio, Francesco AU - Di Virgilio F AD - Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (MicroRNAs) RN - 0 (Purinergic P2X Receptor Antagonists) RN - 0 (Receptors, Purinergic P2X7) SB - IM MH - Adult MH - Animals MH - Apoptosis MH - Biopsy MH - Cell Line, Tumor MH - Cell Proliferation MH - Cytoplasm/metabolism MH - Humans MH - Lung Neoplasms/*metabolism MH - Male MH - Mesothelioma/*metabolism MH - Mesothelioma, Malignant MH - Mice MH - Mice, Nude MH - MicroRNAs/metabolism MH - Pleural Neoplasms/*metabolism MH - Purinergic P2X Receptor Antagonists/*pharmacology MH - Receptors, Purinergic P2X7/*metabolism MH - Signal Transduction PMC - PMC5226537 OTO - NOTNLM OT - P2X7 OT - cancer OT - extracellular ATP OT - mesothelioma OT - purinergic signalling COIS- The Authors declare no conflicts of interest. EDAT- 2016/07/09 06:00 MHDA- 2018/02/24 06:00 PMCR- 2016/08/02 CRDT- 2016/07/09 06:00 PHST- 2015/12/16 00:00 [received] PHST- 2016/06/26 00:00 [accepted] PHST- 2016/07/09 06:00 [pubmed] PHST- 2018/02/24 06:00 [medline] PHST- 2016/07/09 06:00 [entrez] PHST- 2016/08/02 00:00 [pmc-release] AID - 10430 [pii] AID - 10.18632/oncotarget.10430 [doi] PST - ppublish SO - Oncotarget. 2016 Aug 2;7(31):49664-49676. doi: 10.18632/oncotarget.10430.