Role of the P2X7 receptor in <i>in vitro</i> and <i>in vivo</i> glioma tumor growth

Abstract

Human glioblastoma cells are strikingly refractory to ATP-stimulated, P2X7 receptor (P2X7R)-mediated cytotoxicity. To elucidate the mechanistic basis of this feature, we investigated P2X7R-dependent responses in wild type and P2X7R-transfected U138 cells. Mouse GL261 glioma cells were used as an additional control. Here, we report that wild type U138 glioma cells expressed the P2X7R to very low level. Contrary to human U138 cells, mouse GL261 cells showed strong P2X7R expression and P2X7R-dependent responses. Transfection of wild type <i>P2RX7</i> into U138 cells fully restored P2X7R-dependent responses. <i>P2RX7</i> transfection conferred a negligible <i>in vitro</i> growth advantage to U138 cells, while strongly accelerated <i>in vivo</i> growth. <i>In silico</i> analysis showed that the <i>P2RX7</i> gene is seldom mutated in specimens from glioblastoma multiforme (GBM) patients. These observations suggest that the P2X7R might be an important receptor promoting GBM growth.