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.

Insights

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.