REVIEW Extracellular ATP and Cancer—An Overview with Special Reference to P2 Purinergic Receptors Tamás Deli & László Csernoch Received: 17 April 2008 / Accepted: 22 May 2008 / Published online: 25 June 2008 # Arányi Lajos Foundation 2008 Abstract Purinergic signal transduction mechanisms have been appreciated as a complex intercellular signalling network that plays an important regulatory role in both short- and long-term processes in practically every living cell. One of the most intriguing aspects of the field is the participation of ATP and other purine nucleotides in the determination of cell fate and the way they direct cells towards proliferation, differentiation or apoptosis, thereby possibly taking part in promoting or preventing malignant transformation. In this review, following a very brief introduction to the historical aspects of purinergic signal- ling and a concise overview of the structure of and signal transduction pathways coupled to P2 purinergic receptors, the current theories concerning the possible ways how extracellular ATP can alter the function of tumour cells and the effectiveness of anticancer therapies are discussed, including pharmacological, nutritional, vasoactive and ‘anti-antioxidant’ actions of the nucleotide. The effects of ATP on animals inoculated with human tumours and on patients with cancer are looked over next, and then an overview of the literature regarding the expression and presumed functions of P2 purinoceptors on tumour cells in vitro is presented, sorted out according to the relevant special clinical fields. The article is closed by reviewing the latest developments in the diagnostic use of P2 purinergic receptors as tumour markers and prognostic factors, while discussing some of the difficulties and pitfalls of the therapeutic use of ATP analogues. Keywords Extracellular ATP . P2 purinergic receptors . Cancer . Proliferation . Differentiation . Apoptosis Abbreviations ATP adenosine 5′-triphosphate ADP adenosine 5′-diphosphate AMP adenosine 5′-monophosphate PLC phospholipase C IP3 inositol 1,4,5-trisphosphate AC adenylate cyclase cAMP cyclic adenosine monophosphate PKA protein kinase A PCR polymerase chain reaction mRNA messenger ribonucleic acid UTP uridine 5′-triphosphate IL interleukin TNF tumour necrosis factor PSA prostate specific antigen AML acute myelogenous leukaemia ALL acute lymphoblastic leukaemia CML chronic myelogenous leukaemia MDS myelodysplastic syndrome RyR2 ryanodine receptor type 2 Introduction Simultaneously or one after the other, three significant independent functions of adenine compounds have been developed in living cells early in the course of evolution: containing high-energy phosphate groups, adenine com- Pathol. Oncol. Res. (2008) 14:219–231 DOI 10.1007/s12253-008-9071-7 T. Deli : L. Csernoch (*) Department of Physiology, Research Centre for Molecular Medicine, Medical and Health Science Centre, University of Debrecen, 98 Nagyerdei krt., P.O. Box 22, Debrecen 4012, Hungary e-mail: csl@phys.dote.hu T. Deli Department of Obstetrics and Gynaecology, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary