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Open Access Research

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

Mastura Monif1, Terence J O’Brien2, Kate J Drummond3, Christopher A Reid4, Simon V Liubinas3 and David A Williams1*

Author Affiliations

1 Department of Physiology, The University of Melbourne, Melbourne 3010, Victoria, Australia

2 Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne 3010, Victoria, Australia

3 Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Melbourne 3010, Victoria, Australia

4 Howard Florey Institute, The University of Melbourne, Melbourne 3010, Victoria, Australia

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Journal of Inflammation 2014, 11:25  doi:10.1186/s12950-014-0025-4

Published: 28 August 2014

Abstract

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.

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.

Keywords:
Microglia; P2X7; Glioma; Cancer; P2X7 pore