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P2X7 Receptor: the Regulator of Glioma Tumor Development and Survival

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Publisher Springer
Date 2021 Dec 29
PMID 34964926
Citations 8
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Abstract

P2X7 is an ionotropic nucleotide receptor, forming the cation channel upon ATP stimulation. It can also function as a large membrane pore as well as transmit ATP-dependent signal without forming a channel at all. P2X7 activity in somatic cells is well-known, but remains poorly studied in glioma tumors. The current paper presents the comprehensive study of P2X7 activity in C6 and glioma cell line showing the wide range of effects the receptor has on glioma biology. We observed that P2X7 stimulation boosts glioma cell proliferation and increases cell viability. P2X7 activation promoted cell adhesion, mitochondria depolarization, and reactive oxygen species overproduction in C6 cells. P2X7 receptor also influenced glioma tumor growth in vivo via activation of pro-survival signaling pathways and ATP release. Treatment with Brilliant Blue G, a selective P2X7 antagonist, effectively inhibited glioma tumor development; decreased the expression of negative prognostic cancer markers pro-survival and epithelial-mesenchymal transition (EMT)-related proteins; and modulated the immune response toward glioma tumor in vivo. Finally, pathway-specific enrichment analysis of the microarray data from human patients also showed an upregulation of P2X7 receptor in gliomas from grades I to III. The presented results shed more light on the role of P2X7 receptor in the biology of this disease.

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References
1.
Raffaghello L, Chiozzi P, Falzoni S, Di Virgilio F, Pistoia V . The P2X7 receptor sustains the growth of human neuroblastoma cells through a substance P-dependent mechanism. Cancer Res. 2006; 66(2):907-14. DOI: 10.1158/0008-5472.CAN-05-3185. View

2.
Ellert-Miklaszewska A, Poleszak K, Pasierbinska M, Kaminska B . Integrin Signaling in Glioma Pathogenesis: From Biology to Therapy. Int J Mol Sci. 2020; 21(3). PMC: 7037280. DOI: 10.3390/ijms21030888. View

3.
Hambardzumyan D, Gutmann D, Kettenmann H . The role of microglia and macrophages in glioma maintenance and progression. Nat Neurosci. 2015; 19(1):20-7. PMC: 4876023. DOI: 10.1038/nn.4185. View

4.
Chia K, Keatinge M, Mazzolini J, Sieger D . Brain tumours repurpose endogenous neuron to microglia signalling mechanisms to promote their own proliferation. Elife. 2019; 8. PMC: 6685703. DOI: 10.7554/eLife.46912. View

5.
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