Acid-sensing ion channel 1 (ASIC1) mediates weak acid-induced migration of human malignant glioma cells

摘要

Glioblastoma is the most aggressive and lethal tumor in the central nervous system in adult and has poor prognosis due to strong proliferation and aggressive invasion capacity. Acidic microenvironment is commonly observed in tumor tissues but the exact role of acidosis in the pathophysiology of glioblastoma and underlying mechanisms remain unclear. Acid-sensing ion channels (ASICs) are proton-gated cation channels activated by low extracellular pH. Recent studies have suggested that ASICs are involved in the pathogenesis of some tumors, such as lung cancer and breast cancer. But the effect of acidosis and activation of ASICs on malignant glioma of the central nervous system has not been reported. In this study, we investigated the expression of ASIC1 in human glioma cell lines (U87MG and A172) and its possible effect on the proliferation and migration of these cells. The results demonstrated that ASIC1 is functionally expressed in U87MG and A172 cells. Treatment with extracellular weak acid (pH 7.0) has no effect on the proliferation but increases the migration of the two cell lines. Application of PcTX1, a specific inhibitor of ASIC1a and ASIC1a/2b channels, or knocking down ASIC1 by siRNA, can abolish the effect of weak acid-induced cell migration. Together, our results indicate that ASIC1 mediates extracellular weak acid induced migration of human malignant glioma cells and may therefore serve as a therapeutic target for malignant glioma in human.