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We thank the authors for a very thoughtful letter and agree that there are a number of different mechanisms through which isocitrate dehydrogenase (IDH) mutation, the downstream 2-hydroxyglutarate (2HG), can lead to a number of different state changes within tumor cells. The acidification of the tumor microenvironment was solely an interpretation of our Fig. 1. Schematic overview of the proposed effects of mutated IDH1 on cellular metabolism. a-KG is reduced to 2-HG, which when exported out of the cell could lead to acidification of tumor microenvironment. This may promote local invasive growth of tumor cells. We postulate the hypothesis that, because of depletion of cytosolic a-KG, glutamate is imported via EAAT2 and converted to a-KG by GDH (thick arrows). In this way glutamate could act as a chemotactic source that also promotes invasive tumor cell growth. Letters to the editor

Response to "Tumor cells in search for glutamate: an alternative explanation for increased invasiveness of IDH1 mutant gliomas"