Data from Expression of P2X7 Receptor Increases <i>In Vivo</i> Tumor Growth

<div>Abstract<p>The P2X7 receptor is an ATP-gated ion channel known for its cytotoxic activity. However, recent evidence suggests a role for P2X7 in cell proliferation. Here, we found that P2X7 exhibits significant growth-promoting effects <i>in vivo</i>. Human embryonic kidney cells expressing P2X7 exhibited a more tumorigenic and anaplastic phenotype than control cells <i>in vivo</i>, and the growth rate and size of these tumors were significantly reduced by intratumoral injection of the P2X7 inhibitor–oxidized ATP. The accelerated growth of P2X7-expressing tumors was characterized by increased proliferation, reduced apoptosis, and a high level of activated transcription factor NFATc1. These tumors also showed a more developed vascular network than control tumors and secreted elevated amounts of VEGF. The growth and neoangiogenesis of P2X7-expressing tumors was blocked by intratumoral injection of the VEGF-blocking antibody Avastin (bevacizumab), pharmacologic P2X7 blockade, or P2X7 silencing <i>in vivo</i>. Immunohistochemistry revealed strong P2X7 positivity in several human cancers. Together, our findings provide direct evidence that P2X7 promotes tumor growth <i>in vivo</i>. <i>Cancer Res; 72(12); 2957–69. ©2012 AACR</i>.</p></div>