Accelerated tumor progression in mice lacking the ATP receptor P2X7

Research output: Contribution to journalJournal articleResearchpeer-review

Elena Adinolfi, Marina Capece, Alessia Franceschini, Simonetta Falzoni, Anna L Giuliani, Alessandra Rotondo, Alba C Sarti, Massimo Bonora, Susanne Syberg, Domenica Corigliano, Paolo Pinton, Niklas R Jorgensen, Luigi Abelli, Laura Emionite, Lizzia Raffaghello, Vito Pistoia, Francesco Di Virgilio

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.

Original languageEnglish
JournalCancer Research
Volume75
Issue number4
Pages (from-to)635-44
Number of pages10
ISSN0008-5472
DOIs
Publication statusPublished - 15 Feb 2015

    Research areas

  • Adenosine Triphosphate, Animals, Colonic Neoplasms, Gene Expression Regulation, Neoplastic, Humans, Immunity, Innate, Interleukin-1beta, Macrophages, Melanoma, Experimental, Mice, Receptors, Purinergic P2X7, Vascular Endothelial Growth Factor A

ID: 162376987