Katrin Jordan, Evan H. Stanton, Vladimir M. Milenkovic, Marianne Federlin, Konstantin Drexler, Wolfgang Buchalla, Andreas Gaumann, Jerzy Adamski, Martin Proescholdt, Sebastian Haferkamp*, Edward K. Geissler and Maria E. Mycielska* Pages 506 - 513 ( 8 )
Brain tissue is known to have elevated citrate levels, necessary to regulate ion chelation, neuron excitability, and are also necessary for the supply of necessary energy substrates to neurons. Importantly, citrate also acts as a central substrate in cancer metabolism. Recent studies have shown that extracellular citrate levels in the brain undergo significant changes during tumor development and may play a dual role in tumor progression, as well as cancer cell aggressiveness. In the present article, we review available literature describing changes of citrate levels in brain tissue, blood, and cerebrospinal fluid, as well as intracellular alterations during tumor development before and after metastatic progression. Based on the available literature and our recent findings, we hypothesize that changes in extracellular citrate levels may be related to the increased consumption of this metabolite by cancer cells. Interestingly, cancerassociated cells, including reactive astrocytes, might be a source of citrate. Extracellular citrate uptake mechanisms, as well as potential citrate synthesis and release by surrounding stroma, could provide novel targets for anti-cancer treatments of primary brain tumors and brain metastases.
Brain tumor, metabolism, citrate, cancer associated stroma, astrocytes, anti-cancer.
Department of Surgery, University Medical Center Regensburg, Department of Surgery, University Medical Center Regensburg, Department of Psychiatry and Psychotherapy, University of Regensburg, Department of Conservative Dentistry and Periodontology, University Medical Center Regensburg, Regensburg, Department of Dermatology, University Medical Center, Regensburg, Department of Conservative Dentistry and Periodontology, University Medical Center Regensburg, Regensburg, Institute of Pathology, Kaufbeuren-Ravensburg, Kaufbeuren, Molecular Endocrinology and Metabolism, Helmholtz Zentrum Mùˆnchen, German Research Center for Environmental Health, 85764 Neuherberg, Department of Neurosurgery, Regensburg University Hospital, Regensburg, Department of Dermatology, University Medical Center, Regensburg, Department of Surgery, University Medical Center Regensburg, Department of Surgery, University Medical Center Regensburg