The P2X7 receptor, for extracellular ATP, is involved in several signaling pathways, including cell death and inflammation. Recently, it has been demonstrated that P2X7 receptor has a pivotal role both in cancer proliferation and anti-tumoral immune systemactivation (Adinolfi E, et al. Cancer Res. Jun 15;72(12):2957–69. 2012; Ghiringhelli F, et al. Nat Med. Oct;15(10):1170–8. 2009). Although, it’s established that P2X7 receptor expression facilitates in vivo tumor growth, the role of host P2X7 receptor in mouse cancer progression remains unclear. Purpose of this study was to compare primary mass and metastatic progression in WT and P2X7−/− adult male mice. B16-derived melanoma was our election model due to several reasons including: high P2X7 receptor expression, capability to cause both primary and metastatic tumor in syngeneic C57Bl/6 mice, involvement of immune system in melanoma suppression. When subcutaneously injected, P2X7−/− mice showed a tendency to develop bigger primary masses, than WT mice. Thanks to a total body small animal luminometer (IVIS Lumina), we also followed tumor dissemination of B16 cells engineered with an intracellular luciferase, identifying a significantly higher number of lung metastatic colonies in P2X7−/− mice. Indeed, analysis of ex-vivo lungs exhibited a reduced immune infiltrated in P2X7−/− versus WT mice. Our data strongly suggest a role of P2X7 receptor not only on the tumor growth but also in the host responses to melanoma.
Role of P2X7 receptor in host response to melanoma
FRANCESCHINI, Alessia;CAPECE, Marina;ABELLI, Luigi;DI VIRGILIO, Francesco;ADINOLFI, Elena
2014
Abstract
The P2X7 receptor, for extracellular ATP, is involved in several signaling pathways, including cell death and inflammation. Recently, it has been demonstrated that P2X7 receptor has a pivotal role both in cancer proliferation and anti-tumoral immune systemactivation (Adinolfi E, et al. Cancer Res. Jun 15;72(12):2957–69. 2012; Ghiringhelli F, et al. Nat Med. Oct;15(10):1170–8. 2009). Although, it’s established that P2X7 receptor expression facilitates in vivo tumor growth, the role of host P2X7 receptor in mouse cancer progression remains unclear. Purpose of this study was to compare primary mass and metastatic progression in WT and P2X7−/− adult male mice. B16-derived melanoma was our election model due to several reasons including: high P2X7 receptor expression, capability to cause both primary and metastatic tumor in syngeneic C57Bl/6 mice, involvement of immune system in melanoma suppression. When subcutaneously injected, P2X7−/− mice showed a tendency to develop bigger primary masses, than WT mice. Thanks to a total body small animal luminometer (IVIS Lumina), we also followed tumor dissemination of B16 cells engineered with an intracellular luciferase, identifying a significantly higher number of lung metastatic colonies in P2X7−/− mice. Indeed, analysis of ex-vivo lungs exhibited a reduced immune infiltrated in P2X7−/− versus WT mice. Our data strongly suggest a role of P2X7 receptor not only on the tumor growth but also in the host responses to melanoma.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
