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.

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

Bergamin, Letícia Scussel
Primo
;
Capece, Marina;Salaro, Erica;Sarti, Alba Clara;Falzoni, Simonetta;Di Virgilio, Francesco
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.
2019
Bergamin, Letícia Scussel; Capece, Marina; Salaro, Erica; Sarti, Alba Clara; Falzoni, Simonetta; Pereira, Mery Stéfani Leivas; De Bastiani, Marco Antônio; Scholl, Juliete Nathali; Battastini, Ana Maria O; Di Virgilio, Francesco
File in questo prodotto:
File Dimensione Formato  
27106-1034736-1-PB.pdf

accesso aperto

Descrizione: versione editoriale
Tipologia: Full text (versione editoriale)
Licenza: Creative commons
Dimensione 5.86 MB
Formato Adobe PDF
5.86 MB Adobe PDF Visualizza/Apri

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2421991
Citazioni
  • ???jsp.display-item.citation.pmc??? 16
  • Scopus 29
  • ???jsp.display-item.citation.isi??? ND
social impact