P2X(7): a growth-promoting receptor-implications for cancer
Francesco Di Virgilio1, Davide Ferrari, Elena Adinolfi
1Department of Experimental and Diagnostic Medicine, Section of General Pathology, and Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Via Borsari 46, Ferrara, 44100, Italy, fdv@unife.it.
Purinergic Signalling
|March 6, 2009
Summary
The P2X(7) receptor, often seen as cytotoxic, actually promotes cell survival and growth. This finding challenges previous views and suggests new anti-cancer strategies.
Area of Science:
- Cell Biology
- Molecular Pharmacology
- Immunology
Background:
- The P2X(7) receptor is traditionally considered a cytotoxic nucleotide receptor.
- Cytotoxicity is typically observed under sustained pharmacological stimulation, unlikely in physiological conditions.
Purpose of the Study:
- To re-evaluate the role of the P2X(7) receptor in cell physiology.
- To investigate the P2X(7) receptor's function in cell survival and proliferation.
Main Methods:
- Investigated P2X(7) receptor activity in peripheral T lymphocytes and various cell lines.
- Utilized P2X(7) transfection to assess growth advantage and mitochondrial activity.
- Examined P2X(7) modulation in lipopolysaccharide-treated microglia.
- Correlated P2X(7) expression and ATP levels in tumor tissues.
Main Results:
- Extracellular ATP and benzoyl ATP promote T lymphocyte proliferation via P2X(7).
- P2X(7) transfection enhances cell growth and mitochondrial metabolism in HEK293 cells.
- P2X(7) down-modulation is linked to LPS-induced microglia growth arrest.
- High P2X(7) expression and interstitial ATP levels are observed in malignant tumors.
Conclusions:
- The P2X(7) receptor primarily functions as a survival and growth-promoting receptor, not a cytotoxic one.
- Mitochondria play a crucial role in P2X(7)-mediated growth promotion.
- Understanding P2X(7) in cell proliferation may offer novel anti-tumor therapies.
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