P2X7 receptor: the regulator of glioma tumor development and survival

Matyśniak, Damian; Nowak, Natalia; Kukla, Artur; Lehka, Lilya; Oslislok, Magdalena; Pomorski, Paweł

doi:10.1007/s11302-021-09834-2

Cited by 14 publications

(4 citation statements)

References 85 publications

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“…Collectively, this supports a role for P2X7 in glioma development as indicated for human P2X7 (Bergamin, et al, 2019, Kan, et al, 2020, Matyśniak, et al, 2022. However, reduced P2X7 activity is typically associated with reduced glioma progression, so it remains unclear how the potential partial J o u r n a l P r e -p r o o f loss-of-function mutation F103L promotes glioma development in dogs.…”

Section: Polymorphic Variants Of Canine P2x Receptorssupporting

confidence: 55%

P2X receptors: Insights from the study of the domestic dog

2023

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Section: Polymorphic Variants Of Canine P2x Receptorssupporting

confidence: 55%

P2X receptors: Insights from the study of the domestic dog

2023

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“…P2X7R has been shown to increase cellular lactate output and glycogen storage, as well as upregulate glycolytic enzymes, enhancing the ability of tumour cells to adapt to unfavourable ambient conditions 58 . Enhanced mitochondrial depolarisation has also been observed in C6 glioma cells following P2X7R activation 59 . There seems to be a clear metabolic association with P2X7R stimulation.…”

Section: Discussionmentioning

confidence: 89%

P2X7 receptor antagonism by AZ10606120 significantly reduced in vitro tumour growth in human glioblastoma

Kan

Drill

Jayakrishnan

et al. 2023

Sci Rep

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Glioblastomas are highly aggressive and deadly brain tumours, with a median survival time of 14–18 months post-diagnosis. Current treatment modalities are limited and only modestly increase survival time. Effective therapeutic alternatives are urgently needed. The purinergic P2X7 receptor (P2X7R) is activated within the glioblastoma microenvironment and evidence suggests it contributes to tumour growth. Studies have implicated P2X7R involvement in a range of neoplasms, including glioblastomas, although the roles of P2X7R in the tumour milieu remain unclear. Here, we report a trophic, tumour-promoting role of P2X7R activation in both patient-derived primary glioblastoma cultures and the U251 human glioblastoma cell line, and demonstrate its inhibition reduces tumour growth in vitro. Primary glioblastoma and U251 cell cultures were treated with the specific P2X7R antagonist, AZ10606120 (AZ), for 72 h. The effects of AZ treatment were also compared to cells treated with the current first-line chemotherapeutic drug, temozolomide (TMZ), and a combination of both AZ and TMZ. P2X7R antagonism by AZ significantly depleted glioblastoma cell numbers compared to untreated cells, in both primary glioblastoma and U251 cultures. Notably, AZ treatment was more effective at tumour cell killing than TMZ. No synergistic effect between AZ and TMZ was observed. AZ treatment also significantly increased lactate dehydrogenase release in primary glioblastoma cultures, suggesting AZ-induced cellular cytotoxicity. Our results reveal a trophic role of P2X7R in glioblastoma. Importantly, these data highlight the potential for P2X7R inhibition as a novel and effective alternative therapeutic approach for patients with lethal glioblastomas.

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“…Within the P2XR subclass, the P2X 7 R subtype is perhaps the most well studied in regard to cancer pathogenesis ( Di Virgilio et al, 2021 ; Hreich et al, 2021 ; Matyśniak et al, 2021 ). Regarding proliferation, it has been shown that the P2X 7 R subtype initiates an intracellular phosphorylation cascade resulting in the activation of the PI3K/Akt and ERK1/2 pathways, key regulators of cancer survival ( Amoroso et al, 2015 ; Salahuddin et al, 2021 ).…”

Section: Purinoreceptorsmentioning

confidence: 99%

Ligand-Gated Ion Channels as Targets for Treatment and Management of Cancers

et al. 2022

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Ligand-gated ion channels are an ionotropic receptor subtype characterized by the binding of an extracellular ligand, followed by the transient passage of ions through a transmembrane pore. Ligand-gated ion channels are commonly subcategorized into three superfamilies: purinoreceptors, glutamate receptors, and Cys-loop receptors. This classification is based on the differing topographical morphology of the receptors, which in turn confers functional differences. Ligand-gated ion channels have a diverse spatial and temporal expression which implicate them in key cellular processes. Given that the transcellular electrochemical gradient is finely tuned in eukaryotic cells, any disruption in this homeostasis can contribute to aberrancies, including altering the activity of pro-tumorigenic molecular pathways, such as the MAPK/ERK, RAS, and mTOR pathways. Ligand-gated ion channels therefore serve as a potential targetable system for cancer therapeutics. In this review, we analyze the role that each of the three ligand-gated ion channel superfamilies has concerning tumor proliferation and as a target for the treatment of cancer symptomatology.

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P2X7 receptor: the regulator of glioma tumor development and survival

Cited by 14 publications

References 85 publications

P2X receptors: Insights from the study of the domestic dog

P2X receptors: Insights from the study of the domestic dog

P2X7 receptor antagonism by AZ10606120 significantly reduced in vitro tumour growth in human glioblastoma

Ligand-Gated Ion Channels as Targets for Treatment and Management of Cancers

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