Ion channels and transporters as glioma-specific targets

University Of Alabama At Birmingham, Birmingham AL

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Abstract

One of the major impediments for the successful treatment of malignant glioma is the unusual ability of glioma cells to disseminate by invasion into healthy brain. Much research effort has focused on understanding the mechanisms underlying cell motility and the cells' interactions with the extracellular matrix environment. Comparatively little, however, is known concerning intrinsic adaptations of glioma cells, which may facilitate cell invasion. Based on our recent findings, we hypothesize that the movement of ions through ion channels and ion transporters aid the growth and dissemination of glioma cells. We suggest that glioma cells show up-regulation of certain C1- and K+ channels not found in normal glia which allow them to rapidly adjust their cell shape and cell volume thereby facilitating cell invasion. Importantly, these channels allow for the secretion of KCI along with water. The resulting cycle of cell shrinkage and subsequent restoration of cell volume enables cells to navigate the tortuous extracellular spaces in brain. In addition, we hypothesize that glioma cells utilizes a cystine-glutamate transporter that releases neurotoxic glutamate to actively kill peritumoral tissue and provide room for tumor growth. In this proposal, we have developed 3 testable hypotheses, which seek to delineate the specific contribution of ion channels and ion transporters to glioma cell invasion and tumor growth.