American Association for Cancer Research
00085472can141259-sup-130642_1_supp_0_ngdwlv.png (4.4 MB)

Figure S3 from Accelerated Tumor Progression in Mice Lacking the ATP Receptor P2X7

Download (4.4 MB)
posted on 2023-03-30, 23:31 authored by 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

Figure S3. Effect of P2X7R deletion on VEGF release. A, in vitro VEGF release from wt or P2X7R-silenced B16 cells. B, intra-tumor VEGF content of B16-wt or P2X7R-silenced tumors grown in wt or P2X7R-KO mice. VEGF was measured by ELISA. A, * p < 0.05 for B16 shRNA vs B16-wt. B, * p < 0.05 for P2X7R-wt + B16 shRNA vs P2X7R-wt + B16-wt; {section sign}{section sign} p < 0.01 for P2X7R-KO + B16 shRNA vs P2X7R-KO + B16-wt. C-F, VEGF staining of tumors from P2X7R-KO (C and D) or wt (E and F) mice. Specimens were fixed and stained with the anti-VEGF Ab as described in Materials and Methods.



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. Cancer Res; 75(4); 635–44. ©2014 AACR.