Metabolic partitioning in the brain and its hijacking by glioblastoma
- Jed de Ruiter Swain1,2,
- Evdokia Michalopoulou1,
- Evan K. Noch3,
- Michael J. Lukey1 and
- Linda Van Aelst1
- 1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
- 2Cold Spring Harbor Laboratory School of Biological Sciences, Cold Spring Harbor, New York 11724, USA;
- 3Department of Neurology, Division of Neuro-oncology, Weill Cornell Medicine, New York, New York 10021, USA
- Corresponding authors: vanaelst{at}cshl.edu, lukey{at}cshl.edu
Abstract
The different cell types in the brain have highly specialized roles with unique metabolic requirements. Normal brain function requires the coordinated partitioning of metabolic pathways between these cells, such as in the neuron–astrocyte glutamate–glutamine cycle. An emerging theme in glioblastoma (GBM) biology is that malignant cells integrate into or “hijack” brain metabolism, co-opting neurons and glia for the supply of nutrients and recycling of waste products. Moreover, GBM cells communicate via signaling metabolites in the tumor microenvironment to promote tumor growth and induce immune suppression. Recent findings in this field point toward new therapeutic strategies to target the metabolic exchange processes that fuel tumorigenesis and suppress the anticancer immune response in GBM. Here, we provide an overview of the intercellular division of metabolic labor that occurs in both the normal brain and the GBM tumor microenvironment and then discuss the implications of these interactions for GBM therapy.
Keywords
- brain metabolism
- cancer metabolism
- glioblastoma
- glioma
- glioma therapy
- IDH mutation
- immune suppression
- tumor microenvironment
Footnotes
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.350693.123.
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