Glioblastoma cancer stem cell lines express functional acid sensing ion channels ASIC1a and ASIC3. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Tian, Yuemin; Bresenitz, Pia; Reska, Anna; El Moussaoui, Laila; Beier, Christoph; Gründer, Stefan
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 14
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-13666-9
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Acidic microenvironment is commonly observed in tumour tissues, including glioblastoma (GBM), the most aggressive and lethal brain tumour in adults. Acid sensing ion channels (ASICs) are neuronal voltage-insensitive sodium channels, which are sensors of extracellular protons. Here we studied and functionally characterized ASICs in two primary glioblastoma stem cell lines as cell culture models. We detected transcripts of theACCN2 andACCN3 genes, coding for ASIC1 and ASIC3, respectively, but not transcripts ofACCN1 (coding for ASIC2). Available microarray data confirmed thatACCN1 is downregulated in glioma. Western blotting confirmed expression of ASIC1 and ASIC3, the most proton-sensitive ASICs, in both GBM cell lines. We characterized ASICs functionally using whole-cell patch clamp and detected different types of acid-sensitive currents. Some of these currents had kinetics typical for ASICs and were sensitive to specific toxin inhibitors of ASIC1a or ASIC3, demonstrating that the GBM cell lines express functional ASIC1a and ASIC3 that may enable GBM cells to sensitively detect extracellular pH in a tumour tissue. Microarray data revealed that expression ofACCN2 andACCN3 is associated with improved survival of patients suffering from gliomas, suggesting that preserved susceptibility to extracellular pH may impair tumour growth.