Oncotarget

Research Papers:

Role of the P2X7 receptor in in vitro and in vivo glioma tumor growth

Letícia Scussel Bergamin, Marina Capece, Erica Salaro, Alba Clara Sarti, Simonetta Falzoni, Mery Stéfani Leivas Pereira, Marco Antônio De Bastiani, Juliete Nathali Scholl, Ana Maria O. Battastini _ and Francesco Di Virgilio _

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Oncotarget. 2019; 10:4840-4856. https://doi.org/10.18632/oncotarget.27106

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Abstract

Letícia Scussel Bergamin1,2,3, Marina Capece3, Erica Salaro3, Alba Clara Sarti3, Simonetta Falzoni3, Mery Stéfani Leivas Pereira1, Marco Antônio De Bastiani1, Juliete Nathali Scholl1, Ana Maria O. Battastini1 and Francesco Di Virgilio3

1 Graduate Program in Biological Sciences/Biochemistry, Institute of Basic Health Sciences and Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

2 CAPES Foundation, Ministry of Education of Brazil, Brasília DF, Brazil

3 Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy

Correspondence to:

Francesco Di Virgilio,email: fdv@unife.it
Ana Maria O. Battastini,email: abattastini@gmail.com

Keywords: cancer; glioma; P2X7R; purinergic signaling; extracellular ATP

Received: September 10, 2018     Accepted: June 29, 2019     Published: August 06, 2019

ABSTRACT

Human glioblastoma cells are strikingly refractory to ATP-stimulated, P2X7 receptor (P2X7R)-mediated cytotoxicity. To elucidate the mechanistic basis of this feature, we investigated P2X7R-dependent responses in wild type and P2X7R-transfected U138 cells. Mouse GL261 glioma cells were used as an additional control. Here, we report that wild type U138 glioma cells expressed the P2X7R to very low level. Contrary to human U138 cells, mouse GL261 cells showed strong P2X7R expression and P2X7R-dependent responses. Transfection of wild type P2RX7 into U138 cells fully restored P2X7R-dependent responses. P2RX7 transfection conferred a negligible in vitro growth advantage to U138 cells, while strongly accelerated in vivo growth. In silico analysis showed that the P2RX7 gene is seldom mutated in specimens from glioblastoma multiforme (GBM) patients. These observations suggest that the P2X7R might be an important receptor promoting GBM growth.


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