Department of Chemistry, Biology and Biotechnology, University of Perugia, Perugia, Italy.
Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
Rev Physiol Biochem Pharmacol. 2021;181:223-267. doi: 10.1007/112_2020_44.
Brain tumors come in many types and differ greatly in outcome. They are classified by the cell of origin (astrocytoma, ependymoma, meningioma, medulloblastoma, glioma), although more recently molecular markers are used in addition to histology. Brain tumors are graded (from I to IV) to measure their malignancy. Glioblastoma, one of the most common adult primary brain tumors, displays the highest malignancy (grade IV), and median survival of about 15 months. Main reasons for poor outcome are incomplete surgical resection, due to the highly invasive potential of glioblastoma cells, and chemoresistance that commonly develops during drug treatment. An important role in brain tumor malignancy is played by ion channels. The Ca-activated K channels of large and intermediate conductance, KCa3.1 and KCa1.1, and the volume-regulated anion channel, whose combined activity results in the extrusion of KCl and osmotic water, control cell volume, and in turn migration, invasion, and apoptotic cell death. The transient receptor potential (TRP) channels and low threshold-activated Ca (T-type) channels have equally critical role in brain tumor malignancy, as dysregulated Ca signals heavily impact on glioma cell proliferation, migration, invasion. The review provides an overview of the current evidence involving these channels in brain tumor malignancy, and the application of these insights in the light of future prospects for experimental and clinical practice.
脑肿瘤有多种类型，其预后差异很大。它们根据起源细胞（星形细胞瘤、室管膜瘤、脑膜瘤、髓母细胞瘤、神经胶质瘤）进行分类，尽管最近除了组织学之外，还使用分子标志物。脑肿瘤分级（从 I 级到 IV 级）以衡量其恶性程度。胶质母细胞瘤是最常见的成人原发性脑肿瘤之一，显示出最高的恶性程度（IV 级），中位生存时间约为 15 个月。预后不良的主要原因是由于胶质母细胞瘤细胞具有高度侵袭性，手术切除不完全，以及在药物治疗过程中通常会产生的化疗耐药性。离子通道在脑肿瘤恶性程度中起着重要作用。大电导和中电导 Ca 激活的 K 通道，KCa3.1 和 KCa1.1，以及体积调节阴离子通道，其联合活性导致 KCl 和渗透水的排出，控制细胞体积，进而控制迁移、侵袭和细胞凋亡。瞬时受体电位 (TRP) 通道和低阈值激活的 Ca（T 型）通道在脑肿瘤恶性程度中同样具有至关重要的作用，因为失调的 Ca 信号会严重影响神经胶质瘤细胞的增殖、迁移和侵袭。该综述概述了涉及这些通道在脑肿瘤恶性程度中的当前证据，并根据实验和临床实践的未来前景，探讨了这些发现的应用。
