P2X7 receptor: the regulator of glioma tumor development and survival
Damian Matyśniak1, Vira Chumak1,2, Natalia Nowak3
1Laboratory of Molecular Basis of Cell Motility, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Str., 02-093, Warsaw, Poland.
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.
Insights
The P2X7 receptor promotes glioma cell growth and survival. Blocking P2X7 with Brilliant Blue G inhibits tumor development and alters immune response, suggesting P2X7 as a therapeutic target for glioma.
Area of Science:
- Neuroscience
- Oncology
- Cell Biology
Background:
- P2X7 receptor (P2X7) is an ionotropic nucleotide receptor involved in cell signaling.
- While P2X7 activity is known in somatic cells, its role in glioma tumors is understudied.
Purpose of the Study:
- To comprehensively investigate the role and activity of P2X7 in glioma biology.
- To evaluate P2X7 as a potential therapeutic target in glioma.
Main Methods:
- In vitro studies using C6 and glioma cell lines.
- In vivo studies involving glioma tumor models.
- Treatment with P2X7 antagonist Brilliant Blue G.
- Microarray analysis of human glioma patient data.
Main Results:
- P2X7 stimulation enhanced glioma cell proliferation, viability, adhesion, and reactive oxygen species production.
- P2X7 activation promoted glioma tumor growth in vivo via pro-survival pathways and ATP release.
- Brilliant Blue G treatment inhibited tumor development, reduced negative prognostic markers, and modulated immune response.
- Human glioma tissues (grades I-III) showed P2X7 receptor upregulation.
Conclusions:
- P2X7 receptor plays a significant role in glioma biology, promoting tumor growth and survival.
- Targeting P2X7 with antagonists like Brilliant Blue G shows therapeutic potential for glioma treatment.
- P2X7 modulation impacts tumor progression, prognostic markers, and immune response in glioma.
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