Endogenous GAB AA receptor activity suppresses glioma growth

Although genome alterations driving glioma by fueling cell malignancy have largely been resolved, less is known of the impact of tumor environment on disease progression. Here, we demonstrate functional GABA receptor-activated currents in human glioblastoma cells and show the existence of a continuo...

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Bibliographic Details
Published in:Oncogene 2017-02, Vol.36 (6), p.777
Main Authors: Blanchart, A, Fernando, R, Häring, M, Assaife-Lopes, N, Romanov, R A, Andäng, M, Harkany, T, Ernfors, P
Format: Article
Language:English
Subjects:
Animals
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Cell Growth Processes - physiology
Cell Line, Tumor
Glioma - metabolism
Glioma - pathology
Humans
Mice
Receptors, GABA-A - metabolism
Signal Transduction
Tumor Cells, Cultured
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Summary:Although genome alterations driving glioma by fueling cell malignancy have largely been resolved, less is known of the impact of tumor environment on disease progression. Here, we demonstrate functional GABA receptor-activated currents in human glioblastoma cells and show the existence of a continuous GABA signaling within the tumor cell mass that significantly affects tumor growth and survival expectancy in mouse models. Endogenous GABA released by tumor cells, attenuates proliferation of the glioma cells with enriched expression of stem/progenitor markers and with competence to seed growth of new tumors. Our results suggest that GABA levels rapidly increase in tumors impeding further growth. Thus, shunting chloride ions by a maintained local GABA receptor activity within glioma cells has a significant impact on tumor development by attenuating proliferation, reducing tumor growth and prolonging survival, a mechanism that may have important impact on therapy resistance and recurrence following tumor resection.
ISSN:1476-5594
DOI:10.1038/onc.2016.245