Ion Channels in Glioma Malignancy
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 tumo
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Ion Channels in Glioma Malignancy Luigi Catacuzzeno, Luigi Sforna, Vincenzo Esposito, Cristina Limatola, and Fabio Franciolini
Contents 1 Brain Tumors 2 Biological Processes Involved in Brain Tumor Malignancy 2.1 Cell Migration and Invasion 2.2 Cell Cycle and Cell Proliferation 2.3 Apoptosis 2.4 Cell Volume Regulation 2.5 Ca2+ Signaling 3 Ion Channels Primarily Involved in Glioma Malignancy 3.1 Ca2+-Activated K+ Channels 3.2 Cl Channels 3.3 TRP Channels 3.4 Low-Threshold (T-Type) Voltage-Activated Calcium Channels 4 Targeting Ion Channels as Therapeutic Adjuvant in Brain Tumors References
Abstract 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
L. Catacuzzeno (*), L. Sforna, and F. Franciolini Department of Chemistry, Biology and Biotechnology, University of Perugia, Perugia, Italy e-mail: [email protected] V. Esposito Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy C. Limatola Department of Physiology and Pharmacology, Sapienza University of Rome, Laboratory Associated to Istituto Pasteur Italia, Rome, Italy IRCCS Neuromed, Pozzilli, IS, Italy
L. Catacuzzeno et al.
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 Ca2+-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 Ca2+ 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. Keywords Apoptosis · Brain tumor · Ca2+-activated K channels · Ca2+ signaling · Cell migration · Cell proliferation · Cell volume regulation · Cl channels · Glioma · TRP Channels · T-type Ca Channels
1 Brain Tumors Brain tumors are abnormal masses of tissue within the skull in which cells grow out of control, evade apoptosis, and invade the surrounding healthy parenchyma. They can be divided according to their site of origin into primary, those originating from the brain tissue itself, and metastatic, tumors that
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