Molecular Neurobiology

, Volume 42, Issue 1, pp 89–96

Glioma Cell Death: Cell–Cell Interactions and Signalling Networks

  • H. Anne Leaver
  • Maria Theresa Rizzo
  • Ian R. Whittle


The prognosis for patients with malignant gliomas is poor, but improvements may emerge from a better understanding of the pathophysiology of glioma signalling. Recent therapeutic developments have implicated lipid signalling in glioma cell death. Stress signalling in glioma cell death involves mitochondria and endoplasmic reticulum. Lipid mediators also signal via extrinsic pathways in glioma cell proliferation, migration and interaction with endothelial and microglial cells. Glioma cell death and tumour regression have been reported using polyunsaturated fatty acids in animal models, human ex vivo explants, glioma cell preparations and in clinical case reports involving intratumoral infusion. Cell death signalling was associated with generation of reactive oxygen intermediates and mitochondrial and other signalling pathways. In this review, evidence for mitochondrial responses to stress signals, including polyunsaturated fatty acids, peroxidising agents and calcium is presented. Additionally, evidence for interaction of glioma cells with primary brain endothelial cells is described, modulating human glioma peroxidative signalling. Glioma responses to potential therapeutic agents should be analysed in systems reflecting tumour connectivity and CNS structural and functional integrity. Future insights may also be derived from studies of signalling in glioma-derived tumour stem cells.


Glioma Cell death signalling Mitochondria 



arachidonic acid


serine–threonine protein kinase


CCAAT/enhancer binding protein homologous transcription factor


central nervous system




transmembrane mitochondrial potential


endoplasmic reticulum


extracellular signal-regulated kinase


gamma linolenic acid


growth factors


glial fibrillary acidic protein


ER glucose-regulated protein 78


hydrogen peroxide


inducible nitric oxide synthetase




mitogen-activated protein kinase kinase 1/2


mitochondrial permeability transition pore


pol(ADP-ribosyl) polymerase


peripheral benzodiazepine receptor


platelet-derived growth factor


peripheral benzodiazepine receptor

Plase A2

phospholipase A2


type II protein kinase A


polyunsaturated fatty acids


reactive oxygen intermediates


Toll-like receptor-2


tumour necrosis factor


TNF-related apoptosis-inducing ligand


reactive oxygen intermediates


vascular endothelial cell growth factor receptor


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • H. Anne Leaver
    • 1
    • 2
  • Maria Theresa Rizzo
    • 3
  • Ian R. Whittle
    • 1
  1. 1.Department of Clinical NeurosciencesUniversity of EdinburghEdinburghUK
  2. 2.Cell Biology R&DSNBTS EdinburghEdinburghUK
  3. 3.Signal Transduction LaboratoryMethodist Research InstituteIndianapolisUSA

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