GABA(A)-receptor expression in glioma cells is triggered by contact with neuronal cells.
The expression of functional GABA(A)-receptors in glioma cells correlates with low malignancy of tumours and cell lines from glioma lack these receptors. Here we show that contact with neurons induces the expression of functional GABA(A)-receptors. C6 and F98 glioma cell lines were labelled by recombinant expression of enhanced green fluorescent protein injected into rat brain and studied in acute slices after two to three weeks of tumour growth. The cells responded to GABA or the specific agonist, muscimol with a current typical for GABA(A)-receptors, as studied with the patch-clamp technique. To get insight into the mechanism of GABA(A) receptor induction, the C6 or F98 cells were co-cultured with neurons, astrocytes, oligodendrocytes and microglia. Glioma cells expressed functional GABA(A) receptors within 24 h only in cultures where physical contact to neurons occurred. Activation of GABA(A)-receptors in the co-cultures attenuated glioma cell metabolism while blockade of the receptors increased metabolism. We conclude that with this form of interaction, neurons can influence tumour behaviour in the brain.
Synowitz
M
M
Max Delbrück Center for Molecular Medicine, Cellular Neuroscience, Robert-Rössle-Strasse 10, D-13092 Berlin, Germany.
Ahmann
P
P
Matyash
M
M
Kuhn
S A
SA
Hofmann
B
B
Zimmer
C
C
Kirchhoff
F
F
Kiwit
J C
JC
Kettenmann
H
H
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016380:Brain Tissue Transplantation; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation
D018755:GABA Agonists; D018756:GABA Antagonists; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D049452:Green Fluorescent Proteins