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P2X7 receptor: the regulator of glioma tumor development and survival

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 tumo...

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Autores principales: Matyśniak, Damian, Chumak, Vira, Nowak, Natalia, Kukla, Artur, Lehka, Lilya, Oslislok, Magdalena, Pomorski, Paweł
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850512/
https://www.ncbi.nlm.nih.gov/pubmed/34964926
http://dx.doi.org/10.1007/s11302-021-09834-2
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author Matyśniak, Damian
Chumak, Vira
Nowak, Natalia
Kukla, Artur
Lehka, Lilya
Oslislok, Magdalena
Pomorski, Paweł
author_facet Matyśniak, Damian
Chumak, Vira
Nowak, Natalia
Kukla, Artur
Lehka, Lilya
Oslislok, Magdalena
Pomorski, Paweł
author_sort Matyśniak, Damian
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11302-021-09834-2.
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spelling pubmed-88505122022-02-23 P2X7 receptor: the regulator of glioma tumor development and survival Matyśniak, Damian Chumak, Vira Nowak, Natalia Kukla, Artur Lehka, Lilya Oslislok, Magdalena Pomorski, Paweł Purinergic Signal Original Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11302-021-09834-2. Springer Netherlands 2021-12-29 2022-03 /pmc/articles/PMC8850512/ /pubmed/34964926 http://dx.doi.org/10.1007/s11302-021-09834-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Matyśniak, Damian
Chumak, Vira
Nowak, Natalia
Kukla, Artur
Lehka, Lilya
Oslislok, Magdalena
Pomorski, Paweł
P2X7 receptor: the regulator of glioma tumor development and survival
title P2X7 receptor: the regulator of glioma tumor development and survival
title_full P2X7 receptor: the regulator of glioma tumor development and survival
title_fullStr P2X7 receptor: the regulator of glioma tumor development and survival
title_full_unstemmed P2X7 receptor: the regulator of glioma tumor development and survival
title_short P2X7 receptor: the regulator of glioma tumor development and survival
title_sort p2x7 receptor: the regulator of glioma tumor development and survival
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850512/
https://www.ncbi.nlm.nih.gov/pubmed/34964926
http://dx.doi.org/10.1007/s11302-021-09834-2
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