title: Expression of P2X7 receptor increases in vivo tumor growth.
abstract: The P2X7 receptor is an ATP-gated ion channel known for its cytotoxic activity. However, recent evidence suggests a role for P2X7 in cell proliferation. Here, we found that P2X7 exhibits significant growth-promoting effects in vivo. Human embryonic kidney cells expressing P2X7 exhibited a more tumorigenic and anaplastic phenotype than control cells in vivo, and the growth rate and size of these tumors were significantly reduced by intratumoral injection of the P2X7 inhibitor-oxidized ATP. The accelerated growth of P2X7-expressing tumors was characterized by increased proliferation, reduced apoptosis, and a high level of activated transcription factor NFATc1. These tumors also showed a more developed vascular network than control tumors and secreted elevated amounts of VEGF. The growth and neoangiogenesis of P2X7-expressing tumors was blocked by intratumoral injection of the VEGF-blocking antibody Avastin (bevacizumab), pharmacologic P2X7 blockade, or P2X7 silencing in vivo. Immunohistochemistry revealed strong P2X7 positivity in several human cancers. Together, our findings provide direct evidence that P2X7 promotes tumor growth in vivo.
authors.affiliation: Section of General Pathology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Adinolfi
authors.forename: Lizzia
authors.initials: L
authors.lastname: Raffaghello
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Giuliani
authors.forename: Luigi
authors.initials: L
authors.lastname: Cavazzini
authors.forename: Marina
authors.initials: M
authors.lastname: Capece
authors.forename: Paola
authors.initials: P
authors.lastname: Chiozzi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bianchi
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Virgilio
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D017209:Apoptosis; D000068258:Bevacizumab; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D050778:NFATC Transcription Factors / Q000096:biosynthesis; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D058486:Receptors, Purinergic P2X7 / Q000096:biosynthesis / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D050778:NFATC Transcription Factors; D058486:Receptors, Purinergic P2X7; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C017199:2',3'-dialdehyde ATP; D000255:Adenosine Triphosphate