Purinergic Signalling and Cancer

Overview

Journal Purinergic Signal

Publisher Springer

Date 2013 Jun 26

PMID 23797685

Citations 158

Authors

Geoffrey Burnstock

Francesco Di Virgilio

Affiliations

Soon will be listed here.

Abstract

Receptors for extracellular nucleotides are widely expressed by mammalian cells. They mediate a large array of responses ranging from growth stimulation to apoptosis, from chemotaxis to cell differentiation and from nociception to cytokine release, as well as neurotransmission. Pharma industry is involved in the development and clinical testing of drugs selectively targeting the different P1 nucleoside and P2 nucleotide receptor subtypes. As described in detail in the present review, P2 receptors are expressed by all tumours, in some cases to a very high level. Activation or inhibition of selected P2 receptor subtypes brings about cancer cell death or growth inhibition. The field has been largely neglected by current research in oncology, yet the evidence presented in this review, most of which is based on in vitro studies, although with a limited amount from in vivo experiments and human studies, warrants further efforts to explore the therapeutic potential of purinoceptor targeting in cancer.

Citing Articles

Multiomics insights into BMI-related intratumoral microbiota in gastric cancer.

Liu K, Jiang Z, Ma Y, Xia R, Zheng Y, Yin K Front Cell Infect Microbiol. 2025; 15:1511900.

PMID: 40041144 PMC: 11876552. DOI: 10.3389/fcimb.2025.1511900.

Energy metabolism in health and diseases.

Liu H, Wang S, Wang J, Guo X, Song Y, Fu K Signal Transduct Target Ther. 2025; 10(1):69.

PMID: 39966374 PMC: 11836267. DOI: 10.1038/s41392-025-02141-x.

Volume-regulated anion channels conduct ATP in undifferentiated mammary cells and promote tumorigenesis in xenograft nude mouse.

Furuya K, Hirata H, Kobayashi T, Ishiguro H, Sokabe M Front Cell Dev Biol. 2025; 12:1519642.

PMID: 39882260 PMC: 11774906. DOI: 10.3389/fcell.2024.1519642.

Mechanisms of mitochondrial damage-associated molecular patterns associated with inflammatory response in cardiovascular diseases.

Guan X, Li H, Zhang L, Zhi H Inflamm Res. 2025; 74(1):18.

PMID: 39806203 DOI: 10.1007/s00011-025-01993-x.

Antagonism of the ATP-gated P2X7 receptor inhibits the proliferation of hepatocellular carcinoma cells.

Tantai X, Yang X, Liu X, Yang X Purinergic Signal. 2024; .

PMID: 39549156 DOI: 10.1007/s11302-024-10064-5.

References

Morrone F, Oliveira D, Gamermann P, Stella J, Wofchuk S, Wink M . In vivo glioblastoma growth is reduced by apyrase activity in a rat glioma model. BMC Cancer. 2006; 6:226. PMC: 1592110. DOI: 10.1186/1471-2407-6-226. View

Cowen D, Sanders M, Dubyak G . P2-purinergic receptors activate a guanine nucleotide-dependent phospholipase C in membranes from HL-60 cells. Biochim Biophys Acta. 1990; 1053(2-3):195-203. DOI: 10.1016/0167-4889(90)90014-5. View

Sabala P, Czajkowski R, Przybylek K, Kalita K, Kaczmarek L, Baranska J . Two subtypes of G protein-coupled nucleotide receptors, P2Y(1) and P2Y(2) are involved in calcium signalling in glioma C6 cells. Br J Pharmacol. 2001; 132(2):393-402. PMC: 1572584. DOI: 10.1038/sj.bjp.0703843. View

MacKenzie W, Hoskin D, Blay J . Adenosine inhibits the adhesion of anti-CD3-activated killer lymphocytes to adenocarcinoma cells through an A3 receptor. Cancer Res. 1994; 54(13):3521-6. View

Yasuda Y, Saito M, Yamamura T, Yaguchi T, Nishizaki T . Extracellular adenosine induces apoptosis in Caco-2 human colonic cancer cells by activating caspase-9/-3 via A(2a) adenosine receptors. J Gastroenterol. 2009; 44(1):56-65. DOI: 10.1007/s00535-008-2273-7. View

Ruzsnavszky O, Telek A, Gonczi M, Balogh A, Remenyik E, Csernoch L . UV-B induced alteration in purinergic receptors and signaling on HaCaT keratinocytes. J Photochem Photobiol B. 2011; 105(1):113-8. DOI: 10.1016/j.jphotobiol.2011.07.009. View

Ehrlich Y, Garfield M, DAVIS T, Kornecki E, Chaffee J, Lenox R . Extracellular protein phosphorylation systems in the regulation of neuronal function. Prog Brain Res. 1986; 69:197-208. DOI: 10.1016/s0079-6123(08)61060-2. View

Bowler W, Birch M, Gallagher J, Bilbe G . Identification and cloning of human P2U purinoceptor present in osteoclastoma, bone, and osteoblasts. J Bone Miner Res. 1995; 10(7):1137-45. DOI: 10.1002/jbmr.5650100720. View

Morrone F, Jacques-Silva M, Horn A, Bernardi A, Schwartsmann G, Rodnight R . Extracellular nucleotides and nucleosides induce proliferation and increase nucleoside transport in human glioma cell lines. J Neurooncol. 2003; 64(3):211-8. DOI: 10.1023/a:1025699932270. View

10.

Nakamura K, Yoshikawa N, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo M . Antitumor effect of cordycepin (3'-deoxyadenosine) on mouse melanoma and lung carcinoma cells involves adenosine A3 receptor stimulation. Anticancer Res. 2006; 26(1A):43-7. View

11.

Dubyak G . Extracellular ATP activates polyphosphoinositide breakdown and Ca2+ mobilization in Ehrlich ascites tumor cells. Arch Biochem Biophys. 1986; 245(1):84-95. DOI: 10.1016/0003-9861(86)90192-x. View

12.

Merighi S, Simioni C, Gessi S, Varani K, Mirandola P, Aghazadeh Tabrizi M . A(2B) and A(3) adenosine receptors modulate vascular endothelial growth factor and interleukin-8 expression in human melanoma cells treated with etoposide and doxorubicin. Neoplasia. 2009; 11(10):1064-73. PMC: 2745672. DOI: 10.1593/neo.09768. View

13.

Gessi S, Varani K, Merighi S, Morelli A, Ferrari D, Leung E . Pharmacological and biochemical characterization of A3 adenosine receptors in Jurkat T cells. Br J Pharmacol. 2001; 134(1):116-26. PMC: 1572937. DOI: 10.1038/sj.bjp.0704254. View

14.

Schultze-Mosgau A, Katzur A, Arora K, Stojilkovic S, Diedrich K, Ortmann O . Characterization of calcium-mobilizing, purinergic P2Y(2) receptors in human ovarian cancer cells. Mol Hum Reprod. 2000; 6(5):435-42. DOI: 10.1093/molehr/6.5.435. View

15.

Streitova D, Weiterova L, Hofer M, Hola J, Horvath V, Kozubik A . Effect of adenosine on the growth of human T-lymphocyte leukemia cell line MOLT-4. Cancer Invest. 2007; 25(6):419-26. DOI: 10.1080/07357900701359973. View

16.

Czajkowski R, Lei L, Sabala P, Baranska J . ADP-evoked phospholipase C stimulation and adenylyl cyclase inhibition in glioma C6 cells occur through two distinct nucleotide receptors, P2Y(1) and P2Y(12). FEBS Lett. 2002; 513(2-3):179-83. DOI: 10.1016/s0014-5793(02)02255-x. View

17.

Nakazawa K, Koizumi S, Inoue K . Facilitation by 5-hydroxytryptamine of ATP-activated current in rat pheochromocytoma cells. Pflugers Arch. 1994; 427(5-6):492-9. DOI: 10.1007/BF00374266. View

18.

Koizumi S, Ikeda M, Nakazawa K, Inoue K . Enhancement by zinc of ATP-evoked dopamine release from rat pheochromocytoma PC12 cells. Brain Res. 1995; 673(1):75-82. DOI: 10.1016/0006-8993(94)01404-6. View

19.

Maldonado P, Pimentel V, Negrini L, Morsch V, Schetinger M . Role of the purinergic system in patients with cervical intraepithelial neoplasia and uterine cancer. Biomed Pharmacother. 2012; 66(1):6-11. DOI: 10.1016/j.biopha.2011.09.007. View

20.

Di Virgilio F . Purines, purinergic receptors, and cancer. Cancer Res. 2012; 72(21):5441-7. DOI: 10.1158/0008-5472.CAN-12-1600. View