title: Accelerated tumor progression in mice lacking the ATP receptor P2X7.
abstract: The ATP receptor P2X7 (P2X7R or P2RX7) has a key role in inflammation and immunity, but its possible roles in cancer are not firmly established. In the present study, we investigated the effect of host genetic deletion of P2X7R in the mouse on the growth of B16 melanoma or CT26 colon carcinoma cells. Tumor size and metastatic dissemination were assessed by in vivo calliper and luciferase luminescence emission measurements along with postmortem examination. In P2X7R-deficient mice, tumor growth and metastatic spreading were accelerated strongly, compared with wild-type (wt) mice. Intratumoral IL-1β and VEGF release were drastically reduced, and inflammatory cell infiltration was abrogated nearly completely. Similarly, tumor growth was also greatly accelerated in wt chimeric mice implanted with P2X7R-deficient bone marrow cells, defining hematopoietic cells as a sufficient site of P2X7R action. Finally, dendritic cells from P2X7R-deficient mice were unresponsive to stimulation with tumor cells, and chemotaxis of P2X7R-less cells was impaired. Overall, our results showed that host P2X7R expression was critical to support an antitumor immune response, and to restrict tumor growth and metastatic diffusion.
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Adinolfi
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Capece
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Franceschini
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Falzoni
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Giuliani
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy. KU Leuven, Translational Research Center for Gastrointestinal Disorders, Leuven, Belgium.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rotondo
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy.
authors.forename: Alba C
authors.initials: AC
authors.lastname: Sarti
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bonora
authors.affiliation: Research Center for Ageing and Osteoporosis, Departments of Diagnostics and Medicine, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Syberg
authors.affiliation: Department of Health Sciences, Università della Magna Grecia, Catanzaro, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Corigliano
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
authors.affiliation: Research Center for Ageing and Osteoporosis, Departments of Diagnostics and Medicine, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark.
authors.forename: Niklas R
authors.initials: NR
authors.lastname: Jorgensen
authors.affiliation: Department of Life Sciences and Biotechnology, Section of Biology and Evolution, University of Ferrara, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Abelli
authors.affiliation: Animal Facility, S. Martino Hospital, Genova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Emionite
authors.affiliation: Laboratory of Oncology, Gaslini Hospital, Genova, Italy.
authors.forename: Lizzia
authors.initials: L
authors.lastname: Raffaghello
authors.affiliation: Laboratory of Oncology, Gaslini Hospital, Genova, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy. fdv@unife.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Virgilio
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D053583:Interleukin-1beta / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D058486:Receptors, Purinergic P2X7 / Q000172:deficiency / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D053583:Interleukin-1beta; D058486:Receptors, Purinergic P2X7; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000255:Adenosine Triphosphate