Brain Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Brain Cancer, including details on symptoms, benign and malignant tumors, gliomas, treatment.

A role for glutamate in growth and invasion of primary brain tumors.

Sontheimer H

Department of Neurobiology & Center for Glial Biology in Medicine, The University of Alabama Birmingham, Birmingham, Alabama 35294-0021, USA. sontheimer@uab.edu

The vast majority of primary brain tumors derive from glial cells and are collectively called gliomas. While, they share some genetic mutations with other cancers, they do present with a unique biology and have developed adaptations to meet specific biological needs. Notably, glioma growth is physically restricted by the skull, and, unless normal brain cells are destroyed, tumors cannot expand. To overcome this challenge, glioma cells release glutamate which causes excitotoxic death to surrounding neurons, thereby vacating room for tumor expansion. The released glutamate also explains peritumoral seizures which are a common symptom early in the disease. Glutamate release occurs via system X(c), a cystine-glutamate exchanger that releases glutamate in exchange for cystine being imported for the synthesis of the cellular antioxidant GSH. It protects tumor cells from endogenously produced reactive oxygen and nitrogen species but also endows tumors with an enhanced resistance to radiation- and chemotherapy. Pre-clinical data demonstrates that pharmacological inhibition of system X(c) causes GSH depletion which slows tumor growth and curtails tumor invasion in vivo. An Food and Drug Administration approved drug candidate is currently being introduced into clinical trials for the treatment of malignant glioma.

Published 3 April 2008 in J Neurochem, 105(2): 287-95.
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