Abstract |
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 in vivo. Human embryonic kidney cells expressing P2X7 exhibited a more tumorigenic and anaplastic phenotype than control cells in vivo, 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 in vivo. Immunohistochemistry revealed strong P2X7 positivity in several human cancers. Together, our findings provide direct evidence that P2X7 promotes tumor growth in vivo.
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Authors | Elena Adinolfi, Lizzia Raffaghello, Anna Lisa Giuliani, Luigi Cavazzini, Marina Capece, Paola Chiozzi, Giovanna Bianchi, Guido Kroemer, Vito Pistoia, Francesco Di Virgilio |
Journal | Cancer research
(Cancer Res)
Vol. 72
Issue 12
Pg. 2957-69
(Jun 15 2012)
ISSN: 1538-7445 [Electronic] United States |
PMID | 22505653
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal, Humanized
- Biomarkers, Tumor
- NFATC Transcription Factors
- Receptors, Purinergic P2X7
- Vascular Endothelial Growth Factor A
- Bevacizumab
- 2',3'-dialdehyde ATP
- Adenosine Triphosphate
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Topics |
- Adenosine Triphosphate
(analogs & derivatives, pharmacology)
- Animals
- Antibodies, Monoclonal, Humanized
(pharmacology)
- Apoptosis
- Bevacizumab
- Biomarkers, Tumor
- Cell Line, Tumor
- Cell Proliferation
- Cell Transformation, Neoplastic
- Female
- Gene Expression Regulation, Neoplastic
- HEK293 Cells
- Humans
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Nude
- NFATC Transcription Factors
(biosynthesis)
- Neoplasms, Experimental
(blood supply, metabolism, pathology)
- Neovascularization, Pathologic
- Receptors, Purinergic P2X7
(biosynthesis, metabolism)
- Vascular Endothelial Growth Factor A
(antagonists & inhibitors, metabolism)
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