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.
Accelerated Tumor Progression in Mice Lacking the ATP Receptor P2X7
ADINOLFI, ElenaCo-primo
;CAPECE, MarinaCo-primo
;FRANCESCHINI, Alessia;FALZONI, Simonetta;GIULIANI, Anna Lisa;SARTI, Alba Clara;BONORA, Massimo;PINTON, Paolo;ABELLI, Luigi;DI VIRGILIO, Francesco
Ultimo
2015
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.File | Dimensione | Formato | |
---|---|---|---|
Cancer Res-2015-Adinolfi-635-44.pdf
accesso aperto
Descrizione: Full text editoriale
Tipologia:
Full text (versione editoriale)
Licenza:
PUBBLICO - Pubblico con Copyright
Dimensione
2.9 MB
Formato
Adobe PDF
|
2.9 MB | Adobe PDF | Visualizza/Apri |
fulltext.pdf
accesso aperto
Descrizione: Post print
Tipologia:
Post-print
Licenza:
PUBBLICO - Pubblico con Copyright
Dimensione
5.69 MB
Formato
Adobe PDF
|
5.69 MB | Adobe PDF | Visualizza/Apri |
I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.