P2X7 receptors are a potential novel target for anti-glioma therapies

Mastura Monif, Terence J. O'Brien, Kate J. Drummond, Christopher A. Reid, Simon V. Liubinas, David A. Williams

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Results: We reveal human glioma cultures to contain microglia in close association with glioma (tumour) cells. Both glioma cells and microglia were found to express the purinergic, ATP sensing, P2X7R. P2X7R protein expression was increased in microglia derived from tumour when compared to 'peri-tumour' tissue. The pore capacity of P2X7R in tumour-associated microglia was functional, as evidenced by dye uptake experiments. Importantly, inhibition of P2X7R with the synthetic antagonist, brilliant blue G (BBG) resulted in a significant decrease in the number of glioma cells in culture.

Conclusions: P2X7R was found to be over-expressed in grade IV human gliomas and its pore capacity was functional. Antagonism of P2X7R with BBG resulted in a decrease in tumour cell number. This identifies P2X7R as a promising therapeutic target to combat human glioma proliferation.

Background: Human gliomas pose significant morbidity and mortality to those afflicted by them, and currently there are no curative treatment modalities available for these highly invasive tumours.

Methods. With the approval from the human ethics committee, patients diagnosed with brain tumour (glioma) were recruited for this study. At the time of surgical resection, freshly resected tumour as well as 'peri-tumour' tissue were taken directly from theatre to the laboratory and were successfully cultured. Confocal fluorescence microscopy techniques and immunohistochemistry were used for characterization of human glioma cultures. Dye uptake experiments and confocal microscopy were utilized for P2X7 receptor (P2X7R) pore activity.

Original languageEnglish
Article number25
Number of pages10
JournalJournal of Inflammation
Volume11
Issue number1
DOIs
Publication statusPublished - 28 Aug 2014
Externally publishedYes

Keywords

  • Cancer
  • Glioma
  • Microglia
  • P2X7
  • P2X7 pore

Cite this

Monif, Mastura ; O'Brien, Terence J. ; Drummond, Kate J. ; Reid, Christopher A. ; Liubinas, Simon V. ; Williams, David A. / P2X7 receptors are a potential novel target for anti-glioma therapies. In: Journal of Inflammation. 2014 ; Vol. 11, No. 1.
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abstract = "Results: We reveal human glioma cultures to contain microglia in close association with glioma (tumour) cells. Both glioma cells and microglia were found to express the purinergic, ATP sensing, P2X7R. P2X7R protein expression was increased in microglia derived from tumour when compared to 'peri-tumour' tissue. The pore capacity of P2X7R in tumour-associated microglia was functional, as evidenced by dye uptake experiments. Importantly, inhibition of P2X7R with the synthetic antagonist, brilliant blue G (BBG) resulted in a significant decrease in the number of glioma cells in culture.Conclusions: P2X7R was found to be over-expressed in grade IV human gliomas and its pore capacity was functional. Antagonism of P2X7R with BBG resulted in a decrease in tumour cell number. This identifies P2X7R as a promising therapeutic target to combat human glioma proliferation.Background: Human gliomas pose significant morbidity and mortality to those afflicted by them, and currently there are no curative treatment modalities available for these highly invasive tumours.Methods. With the approval from the human ethics committee, patients diagnosed with brain tumour (glioma) were recruited for this study. At the time of surgical resection, freshly resected tumour as well as 'peri-tumour' tissue were taken directly from theatre to the laboratory and were successfully cultured. Confocal fluorescence microscopy techniques and immunohistochemistry were used for characterization of human glioma cultures. Dye uptake experiments and confocal microscopy were utilized for P2X7 receptor (P2X7R) pore activity.",
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P2X7 receptors are a potential novel target for anti-glioma therapies. / Monif, Mastura; O'Brien, Terence J.; Drummond, Kate J.; Reid, Christopher A.; Liubinas, Simon V.; Williams, David A.

In: Journal of Inflammation, Vol. 11, No. 1, 25, 28.08.2014.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - P2X7 receptors are a potential novel target for anti-glioma therapies

AU - Monif, Mastura

AU - O'Brien, Terence J.

AU - Drummond, Kate J.

AU - Reid, Christopher A.

AU - Liubinas, Simon V.

AU - Williams, David A.

PY - 2014/8/28

Y1 - 2014/8/28

N2 - Results: We reveal human glioma cultures to contain microglia in close association with glioma (tumour) cells. Both glioma cells and microglia were found to express the purinergic, ATP sensing, P2X7R. P2X7R protein expression was increased in microglia derived from tumour when compared to 'peri-tumour' tissue. The pore capacity of P2X7R in tumour-associated microglia was functional, as evidenced by dye uptake experiments. Importantly, inhibition of P2X7R with the synthetic antagonist, brilliant blue G (BBG) resulted in a significant decrease in the number of glioma cells in culture.Conclusions: P2X7R was found to be over-expressed in grade IV human gliomas and its pore capacity was functional. Antagonism of P2X7R with BBG resulted in a decrease in tumour cell number. This identifies P2X7R as a promising therapeutic target to combat human glioma proliferation.Background: Human gliomas pose significant morbidity and mortality to those afflicted by them, and currently there are no curative treatment modalities available for these highly invasive tumours.Methods. With the approval from the human ethics committee, patients diagnosed with brain tumour (glioma) were recruited for this study. At the time of surgical resection, freshly resected tumour as well as 'peri-tumour' tissue were taken directly from theatre to the laboratory and were successfully cultured. Confocal fluorescence microscopy techniques and immunohistochemistry were used for characterization of human glioma cultures. Dye uptake experiments and confocal microscopy were utilized for P2X7 receptor (P2X7R) pore activity.

AB - Results: We reveal human glioma cultures to contain microglia in close association with glioma (tumour) cells. Both glioma cells and microglia were found to express the purinergic, ATP sensing, P2X7R. P2X7R protein expression was increased in microglia derived from tumour when compared to 'peri-tumour' tissue. The pore capacity of P2X7R in tumour-associated microglia was functional, as evidenced by dye uptake experiments. Importantly, inhibition of P2X7R with the synthetic antagonist, brilliant blue G (BBG) resulted in a significant decrease in the number of glioma cells in culture.Conclusions: P2X7R was found to be over-expressed in grade IV human gliomas and its pore capacity was functional. Antagonism of P2X7R with BBG resulted in a decrease in tumour cell number. This identifies P2X7R as a promising therapeutic target to combat human glioma proliferation.Background: Human gliomas pose significant morbidity and mortality to those afflicted by them, and currently there are no curative treatment modalities available for these highly invasive tumours.Methods. With the approval from the human ethics committee, patients diagnosed with brain tumour (glioma) were recruited for this study. At the time of surgical resection, freshly resected tumour as well as 'peri-tumour' tissue were taken directly from theatre to the laboratory and were successfully cultured. Confocal fluorescence microscopy techniques and immunohistochemistry were used for characterization of human glioma cultures. Dye uptake experiments and confocal microscopy were utilized for P2X7 receptor (P2X7R) pore activity.

KW - Cancer

KW - Glioma

KW - Microglia

KW - P2X7

KW - P2X7 pore

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M3 - Article

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