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
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.
CAPES Foundation, Ministry of Education of Brazil, Brasília DF, Brazil.
Oncotarget. 2019 Aug 6;10(47):4840-4856. doi: 10.18632/oncotarget.27106.
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 into U138 cells fully restored P2X7R-dependent responses. transfection conferred a negligible growth advantage to U138 cells, while strongly accelerated growth. analysis showed that the 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.
人胶质母细胞瘤细胞对ATP刺激的、P2X7受体(P2X7R)介导的细胞毒性具有显著的抗性。为了阐明这一特性的机制基础,我们研究了野生型和转染了P2X7R的U138细胞中P2X7R依赖性反应。小鼠GL261胶质瘤细胞用作额外的对照。在此,我们报告野生型U138胶质瘤细胞中P2X7R表达水平极低。与人类U138细胞相反,小鼠GL261细胞表现出强烈的P2X7R表达和P2X7R依赖性反应。将野生型转染到U138细胞中可完全恢复P2X7R依赖性反应。转染赋予U138细胞的生长优势可忽略不计,而强烈加速了生长。分析表明,该基因在多形性胶质母细胞瘤(GBM)患者的标本中很少发生突变。这些观察结果表明,P2X7R可能是促进GBM生长的重要受体。