Accelerated tumor progression in mice lacking the ATP receptor P2X7

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

Research output: Contribution to journalArticle

Abstract

The ATP receptor P2X7 (P2X7R or P2RX7) has a key role in inflammationand 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, comparedwith 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. Cancer Res; 75(4);

Original languageEnglish
Pages (from-to)635-644
Number of pages10
JournalCancer Research
Volume75
Issue number4
DOIs
Publication statusPublished - Feb 15 2015

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Adinolfi, E., Capece, M., Franceschini, A., Falzoni, S., Giuliani, A. L., Rotondo, A., Sarti, A. C., Bonora, M., Syberg, S., Corigliano, D., Pinton, P., Jorgensen, N. R., Abelli, L., Emionite, L., Raffaghello, L., Pistoia, V., & Di Virgilio, F. (2015). Accelerated tumor progression in mice lacking the ATP receptor P2X7. Cancer Research, 75(4), 635-644. https://doi.org/10.1158/0008-5472.CAN-14-1259