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Malignant glioma-induced neuronal cell death in an
organotypic glioma invasion model. Technical note
Eyupoglu IY, Hahnen E, Heckel A, Siebzehnrubl FA, Buslei R, Fahlbusch R,
Blumcke I
Department of Neurosurgery, University of Erlangen-Nuremberg Department of
Neuropathology, University of Erlangen-Nuremberg, Erlangen, Germany.
eyupoglu@gmx.net
Rapid growth and diffuse brain infiltration are hallmarks of malignant
gliomas.
The underlying molecular pathomechanisms of these tumors, however,
remain to be determined.
The authors present a novel glioma invasion model
that allows researchers to monitor consecutively tumor cell proliferation
and migration in an organotypic brain environment.
Enhanced green
fluorescent protein-labeled F98 rat glioma cells were implanted into slice
cultures obtained from a rat hippocampus, and tumor growth was
microscopically documented up to 20 days in vitro.
Invasion along radially
oriented migratory streams could be observed 5 days after implantation of
rat F98, human U87MG, and mouse GL261 glioma cells, whereas human Be(2)c
neuroblastoma cells and mouse HT22 hippocampal neurons failed to invade the
brain parenchyma.
Following implantation of F98 glioma cells into the
entorhinal cortex, cell death was observed within the infiltrated brain
parenchyma as well as in the neuroanatomically connected dentate gyrus.
Application of the N-methyl-D-aspartate receptor antagonist MK801 to the
culture medium significantly reduced neuronal degeneration in the dentate
gyrus, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
receptor antagonist GYKI 52466 inhibited peritumoral cytotoxicity.
This new
model allows researchers to address in a systematic manner the molecular
pathways of brain invasion as well as specific tumor-host interactions such
as necrosis.
PMID: 15871520 [PubMed - in process]
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