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Acta Physiologica 2007; Volume 189, Supplement 653
The 86th Annual Meeting of The German Physiological Society
3/25/2007-3/28/2007
Hannover, Germany


HYPOXIA STIMULATES THE MIGRATION OF NEUROBLASTOMA CELLS THROUGH ACTIVATION OF THE BDNF-TRKB PATHWAY
Abstract number: O08-1

Martens1 LK, Kirschner1 KM, Scholz1 H

1Institut fr Vegetative Physiologie, Charit Universittsmedizin Berlin

The purpose of this study was to explore whether low oxygen stimulates the migration of neuroblastoma cells, and to analyze the potential role of the TrkB neurotrophin receptor in this process. Human neuroblastoma-derived Kelly cells were pre- incubated for 24 hours either at 21 % ("normoxia") or 1 % O2 ("hypoxia"), and cell migration was assayed in transwell chambers at 21 % O2 for 24 hours. The number of migrating cells was almost increased three-fold after exposure at 1 % O2 compared to 21 % O2. Incubation at 1 % O2 stimulated TrkB mRNA and protein expression more than 25-fold through stabilization of the hypoxia-inducible factor-1 (HIF-1). Migration of normoxic and ex-hypoxic Kelly cells was enhanced approx. 2,5-fold in the presence of the TrkB ligand, brain-derived neurotrophic factor (BDNF, 50 ng/ml). Neuroblastoma cells with forced expression of the TrkB receptor had a 4-fold increased migratory capacity compared to non-expressing cells. Cell migration was reduced significantly by the tyrosine kinase inhibitor K252a (200 nmol/l). In conclusion, up-regulation of the TrkB neurotrophin receptor under hypoxia provides a stimulatory signal for neuroblastoma cell migration and may contribute to malignant neuronal tumor growth.

To cite this abstract, please use the following information:
Acta Physiologica 2007; Volume 189, Supplement 653 :O08-1

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