P2X7 receptor supports proliferation and progression of neuroblastoma cells, in vitro

It is largely demonstrated that expression of P2X7 receptor (P2X7R) drives proliferation of tumor cells by modulating NFATc1 pathway via Ca2+ influx (Adinolfi E et al.; J Biol Chem.; 284(15):10120–8. 2009). Moreover P2X7 receptor expression is shown to be tightly related to the re-organization of metabolic pathways for balancing energy generation in restricted metabolites viability, as fast growing tumors need (Amoroso F et al.; Cell Death Dis.; 3:e370. 2012). Neuroblastoma is the most common extra cranial solid tumor in childhood and one of the most aggressive. ACN human neuroblastoma cell line is known to express P2X7 receptor (Raffaghello L et al.; Cancer Res. 66(2):907–14. 2006) and release VEGF in a P2X7 dependent fashion (Adinolfi E et al.; Cancer Res. 72(12):2957–69. 2012).We showhere that basal P2X7 receptor expression leadsACNproliferation, while silencing P2X7 receptor causes a down-modulation of PI3K/HIF1α/GSK3β pathway. Furthermore proliferation and metabolism modulation as well, can be affected by pharmacological treatment of ACN cells with P2X7 antagonists. These data show that P2X7R plays an important role in neuroblastoma tumor progression and adaptation to environmental condition. Thus, we suggest P2X7R as a possible pharmacological target for neuroblastoma treatment.