Due to an increased metabolic rate, an acidic environment is commonly observed in tumor tissues. The acidic environment likely has a significant impact on the viability and proliferation of tumor cells. Acid-sensing ion channel (ASIC)1a is the key proton receptor expressed in nervous systems, which regulates acidosis-induced neuronal injury in various neurological diseases, such as ischemic stroke. Glioblastomamultiforme (GBM) is the most common and aggressive primary brain tumor in adults with median survival time of 14.6 months. Since GBM are characterized by chronic hypoxia and poor perfusion that is likely to result in acidosis, acidosis may influence the growth behavior and response to cytotoxic therapy. In the present study, we examined the effects of acidosis on growth and migration of cultured human malignant glioma cells A172, and the role of ASIC1a in the cell death induced by extracellular acid. Methods: 1) We detected ASIC1a mRNA using reverse-transcription polymerase chain reaction (RT-PCR). 2) We then determined the presence of ASIC1a in A172 cells using electrophysiological recording (patch-clamp technique). 3) We assessed the effects of acidic environment on cell proliferation and maintenance of clonogenic capability using MTT assay and colony formation assay respectively. 4) Finally, we examined the effects of acidic environment on glioma cell migration by transwell invasion assay. Results: 1) RT-PCR detected the presence of ASIC1a and ASIC4 mRNA in A172 cells. 2) The inward current was recorded when treated with pH5.0 solution indicating the expression of functional ASIC1a in A172 cells. 3) Acidic environment decreased the number of surviving A172 cells, the colony formation, and also inhibited A172 cell migration. 4) Inhibition of ASIC currents by nonspecific inhibitor of ASICs amiloride or specific inhibitor PcTX1 protected A172 cell from death. Conclusions: Extracellular acid reduces proliferation and migration in glioma cells. Extracellular acid induces death of glioma cells via ASIC1a mechanisms. These results indicate the presence of ASIC1a in glioma cells and may play significant role in glioma progression. This work was supported by the National Institutes of Health grant numbers NIH R01NS047506, R01NS066027, UL1 RR025008, U54 RR026137, AHA 0840132N, and ALZ IIRG-10-173350.
Citation Format: Mingli Liu, Alyssa (Aihui) Guo, Christopher Ghiathi, Zhigang Xiong. Acid-sensing ion channel 1a (ASIC1a) contributes to cell proliferation and migration caused by acidic environment in human glioma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4058. doi:10.1158/1538-7445.AM2014-4058