Role of adenosine 5' triphosphate in lymphokine activated (LAK) killing of human tumor cells

This paper presents evidence that extracellular ATP is a critical factor involved in human LAK cell-mediated cytotoxicity. A correlation between sensitivity to ATP and LAK cells has been found using a panel of human carcinoma and melanoma cells. This sensitivity was in parallel modulated by pretreatment with phorbol 12-myristate 13-acetate (PMA) or verapamil. Degradation of extracellular ATP by apyrase as well as ADP-β-S, a receptorial antagonist of ATP, abrogated ATP- as well as LAK-mediated cytotoxicity. ATP binding sites have been detected by radioreceptor assays with ADP-β-³⁵S on the cell surface of LAK and ATP sensitive cancer cells. The cytotoxic receptor has been characterized as P2x purine-receptors by a panel of synthetic nucleotides. No nucleotide receptor was detected on the LAK and ATP-resistant cancer cells. These results demonstrate that extracellular ATP is needed for an efficient LAK cell-mediated cytotoxicity and suggest the involvement of P2x receptors in the mechanisms of cell killing.