Abstract
Altered metabolism is a hallmark of cancer cells. Tumor cells rewire their metabolism to support their uncontrolled proliferation by taking up nutrients from the microenvironment. The amino acid glutamine is a key nutrient that fuels biosynthetic processes including ATP generation, redox homeostasis, nucleotide, protein, and lipid synthesis. Glutamine as a precursor for the neurotransmitter glutamate, and plays a critical role in the normal functioning of the brain. Brain tumors that grow in this glutamine/glutamate rich microenvironment can make synaptic connections with glutamatergic neurons and reprogram glutamine metabolism to enable their growth. In this review, we examine the functions of glutamate/glutamine in the brain and how brain tumor cells reprogram glutamine metabolism. Altered glutamine metabolism can be leveraged to develop non-invasive imaging strategies and we review these imaging modalities. Finally, we examine if targeting glutamine metabolism could serve as a therapeutic strategy in brain tumors.
Highlights
Brain tumors in adults and children are challenging tumors to treat
We focus on how brain tumor cells utilize glutamine in the context of this unique microenvironment, and some of the limitations we encounter in studying glutamine metabolism
We examine the potential of targeting glutamine metabolism in brain tumors as novel therapeutic avenues to treat these tumors
Summary
Brain tumors in adults and children are challenging tumors to treat. Aggressive gliomas including glioblastomas (GBM) and high-grade gliomas have very poor outcomes, emphasizing the need to better understand their pathogenesis. Cancer cells can use nutrients such as glucose and the amino acid glutamine to support continuous proliferation and macromolecule biosynthesis These metabolic needs can be regulated by cell-intrinsic mechanisms as well as nutrient availability in the tumor microenvironment [1]. From the perspective of glutamine metabolism and the brain tumor microenvironment, the normal functions of neurons and glial cells is critical to understand. Astrocytes play a key role in maintaining glutamate homeostasis by regulating its synthesis from glucose as well as its recycling from the synapse They are one of the principle components of the brain cytoarchitecture, and mitigate glutamate toxicity by the glutamate/glutamine neuroglial cycle [5], along with other critical functions. Glutamate uptake in astrocytes is mediated through different classes of glutamate transporters that are functionally distinct
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
