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Human melanomas express functional P2 X(7) receptors.
Nicholas White1, Peter E M Butler, Geoffrey Burnstock
1Autonomic Neuroscience Centre, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK.
Cell and Tissue Research
|July 2, 2005
Summary
The P2X7 receptor, activated by extracellular adenosine triphosphate, triggers apoptosis in human malignant melanoma cells. This finding reveals the P2X7 receptor as a potential therapeutic target for melanoma treatment.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Adenosine 5'-triphosphate (ATP) acts as an extracellular messenger through specific cell surface receptors.
- Different receptor subtypes regulate critical cellular functions including proliferation, differentiation, and apoptosis.
Purpose of the Study:
- To investigate the functional expression and apoptotic effects of the P2X7 receptor in human malignant melanoma.
- To explore the P2X7 receptor as a potential therapeutic target for melanoma.
Main Methods:
- Utilized a potent P2X7 receptor agonist (2'-3'-O-(4-benzoyl-benzoyl) adenosine 5'-triphosphate) and antagonist (1-N,O-bis-[5-isoquinoline-sulfonyl]-N-methyl-L-tyrosyl)-4-phenyl-piperazine).
- Confirmed P2X7 receptor synthesis using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and immunocytochemistry.
- Assessed apoptosis via cellular YO-PRO-1 dye uptake.
Main Results:
- P2X7 receptor activation by the agonist resulted in a dose-dependent and reversible decrease in melanoma cell number.
- Evidence confirmed the functional expression of P2X7 receptors in human melanoma cells.
- YO-PRO-1 uptake indicated P2X7 receptor-mediated cell death.
Conclusions:
- P2X7 receptors are functionally expressed in human malignant melanoma.
- Extracellular nucleotides acting via P2X7 receptors induce apoptosis in melanoma cells.
- The P2X7 receptor represents a novel therapeutic target for melanoma.