Artikel
Transferrin receptor mediated iron accumulation controls proliferation and glutamate release in glioma cells
Suche in Medline nach
Autoren
Veröffentlicht: | 20. Mai 2009 |
---|
Gliederung
Text
Objective: To determine whether chemical manipulation of intracellular iron influences malignant behavior of glioma cells.
Methods: Proliferation measurements by BrdU test, ROS level measurements using H2DCFDA, Western blotting, immunoprecipitation, in vivo U373 glioma model, immunofluorescence microscopy.
Results: As we demonstrated previously, altered expression of transferrin receptors in human glioma cells regulated by Ets-1 mediates ROS signaling, proliferation, and migration and thereby enhances glioma progression.
We could show that iron- and oxidant-chelators attenuated tumor-proliferation in vitro and tumor-size in vivo and that the TfR-induced oxidant accumulation modified cellular signaling by inactivating a protein tyrosine phosphatase (LMW-PTP), activating MAPK and Akt, and by inactivating p21/cdkn1a and pRB. Inactivation of these cell cycle regulators facilitated S-phase entry. Besides its effect on proliferation, TfR also boosted glutamate release, which caused NMDA receptor-mediated reduction of neuron cell mass.
Conclusions: The reduction of ROS by chemical chelation reduces glioma proliferation and toxic glutamate release.