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Extracellular ATP and Cancer—An Overview with Special Reference to P2 Purinergic Receptors

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  • Published:
Pathology & Oncology Research

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 signalling 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.

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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

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Authors and Affiliations

  1. 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

    Tamás Deli & László Csernoch

  2. Department of Obstetrics and Gynaecology, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary

    Tamás Deli

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  1. Tamás Deli
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  2. László Csernoch
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Correspondence to László Csernoch.

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Deli, T., Csernoch, L. Extracellular ATP and Cancer—An Overview with Special Reference to P2 Purinergic Receptors. Pathol. Oncol. Res. 14, 219–231 (2008). https://doi.org/10.1007/s12253-008-9071-7

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  • DOI: https://doi.org/10.1007/s12253-008-9071-7

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