Ross Sandra B, Fuller Catherine M, Bubien James K, Benos Dale J
Dept. Physiology and Biophysics, Univ. of Alabama at Birmingham, 1918 University Blvd., MCLM 704, Birmingham, AL 35294-0005, USA.
Am J Physiol Cell Physiol. 2007 Sep;293(3):C1181-5. doi: 10.1152/ajpcell.00066.2007. Epub 2007 Jul 5.
Despite intensive research, brain tumors remain among the most difficult type of malignancies to treat, due largely to their diffusely invasive nature and the associated difficulty of adequate surgical resection. To migrate through the brain parenchyma and to proliferate, glioma cells must be capable of significant changes in shape and volume. We have previously reported that glioma cells express an amiloride- and psalmotoxin-sensitive cation conductance that is not found in normal human astrocytes. In the present study, we investigated the potential role of this ion channel to mediate regulatory volume increase in glioma cells. We found that the ability of the cells to volume regulate subsequent to cell shrinkage by hyperosmolar solutions was abolished by both amiloride and psalmotoxin 1. This toxin is thought to be a specific peptide inhibitor of acid-sensing ion channel (ASIC1), a member of the Deg/ENaC superfamily of cation channels. We have previously shown this toxin to be an effective blocker of the glioma cation conductance. Our data suggest that one potential role for this conductance may be to restore cell volume during the cell's progression thorough the cell cycle and while the tumor cell migrates within the interstices of the brain.
尽管进行了深入研究，但脑肿瘤仍然是最难治疗的恶性肿瘤类型之一，这主要是由于其具有弥漫性浸润的特性以及难以进行充分的手术切除。为了在脑实质中迁移和增殖，胶质瘤细胞必须能够在形状和体积上发生显著变化。我们之前报道过，胶质瘤细胞表达一种对氨氯吡咪和圣毒素敏感的阳离子电导，而正常人类星形胶质细胞中不存在这种电导。在本研究中，我们调查了这种离子通道在介导胶质瘤细胞调节性容积增加中的潜在作用。我们发现，用高渗溶液使细胞收缩后，细胞进行容积调节的能力被氨氯吡咪和圣毒素1均消除。这种毒素被认为是酸敏感离子通道（ASIC1）的一种特异性肽抑制剂，ASIC1是阳离子通道Deg/ENaC超家族的成员。我们之前已表明这种毒素是胶质瘤阳离子电导的有效阻滞剂。我们的数据表明，这种电导的一个潜在作用可能是在细胞通过细胞周期的过程中以及肿瘤细胞在脑间隙内迁移时恢复细胞体积。
