Malignant glioma-induced neuronal cell death in an organotypic glioma invasion model. Technical note.
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.
Eyüpoglu
Ilker Y
IY
Department of Neurosurgery, University of Erlangen-Nuremberg Department of Neuropathology, University of Erlangen-Nuremberg, Erlangen, Germany. eyupoglu@gmx.net
Hahnen
Eric
E
Heckel
Alexandra
A
Siebzehnrübl
Florian A
FA
Buslei
Rolf
R
Fahlbusch
Rudolf
R
Blümcke
Ingmar
I
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001932:Brain Neoplasms / Q000503:physiopathology*; D016923:Cell Death; D002465:Cell Movement; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000473:pathology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005910:Glioma / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D018696:Neuroprotective Agents; C061950:GYKI 52466; D001569:Benzodiazepines; D016291:Dizocilpine Maleate