P2X7 receptor oncogenetic role in immunocompromised and immunocompetent mouse models

In the last decade the role of P2X7 in cell growth and transformation has been studied on in vitro models and patients suggesting a link between receptor over-expression and tumorigenesis (Di Virgilio 2009). Nevertheless, in vivo experiments on animal models were lacking. Here we show that HEK293 cells transfected with human P2X7 (HEK293-P2X7) are more tumorigenic in a nude/nude, immunocompromised, mice model than HEK293 cells transfected with the empty vector (HEK293-mock). HEK293-P2X7 cells generated increased numbers of faster growing tumors. HEK293-P2X7 neoplasms appeared more anaplastic and showed a higher number of blood vessels. According with neo-vascularization data, HEK293-P2X7 secreted increased levels of vascular endothelial growth factor (VEGF) both in vitro and in vivo. Accelerated tumor growth was due to increased proliferation and reduced apoptosis, as shown by augmented Ki67 labeling, and reduced TUNEL staining respectively. Similar results were also obtained in Balb/c immunocompetent mice injected with CT260 colon cancer cells overexpressing mouse P2X7 receptor. This study provides a direct in vivo evidence of the P2X7 growth-promoting activity and points to a role for this receptor in carcinogenesis.