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
Article

DOI: 10.1007/s12035-010-8135-3

Cite this article as:
Leaver, H.A., Rizzo, M.T. & Whittle, I.R. Mol Neurobiol (2010) 42: 89. doi:10.1007/s12035-010-8135-3

Abstract

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.

Keyword

GliomaCell death signallingMitochondria

Abbreviations

AA

arachidonic acid

Akt

serine–threonine protein kinase

CHOP/GADD153

CCAAT/enhancer binding protein homologous transcription factor

CNS

central nervous system

COX

cyclo-oxygenase

ΔΨm

transmembrane mitochondrial potential

ER

endoplasmic reticulum

ERK

extracellular signal-regulated kinase

GLA

gamma linolenic acid

GF

growth factors

GFAP

glial fibrillary acidic protein

GRP78/BiP

ER glucose-regulated protein 78

H2O2

hydrogen peroxide

iNOS

inducible nitric oxide synthetase

LO

lipoxygenase

MEK-1/2

mitogen-activated protein kinase kinase 1/2

MPT

mitochondrial permeability transition pore

PARP

pol(ADP-ribosyl) polymerase

PBR

peripheral benzodiazepine receptor

PDGF

platelet-derived growth factor

PDR

peripheral benzodiazepine receptor

Plase A2

phospholipase A2

PKAII

type II protein kinase A

PUFA

polyunsaturated fatty acids

roi

reactive oxygen intermediates

TLR

Toll-like receptor-2

TNF

tumour necrosis factor

TRAIL

TNF-related apoptosis-inducing ligand

roi

reactive oxygen intermediates

VEGFR

vascular endothelial cell growth factor receptor

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