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Intratumoral Distribution of Lactate and the Monocarboxylate Transporters 1 and 4 in Human Glioblastoma Multiforme and Their Relationships to Tumor Progression-Associated Markers

1
Department of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, 24105 Kiel, Germany
2
Department of Neuroradiology, University Medical Center Schleswig-Holstein, UKSH Campus Kiel, 24105 Kiel, Germany
3
Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel University, 24118 Kiel, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6254; https://doi.org/10.3390/ijms21176254
Received: 14 August 2020 / Accepted: 27 August 2020 / Published: 29 August 2020
(This article belongs to the Section Molecular Oncology)
(1) Background: Metabolic reprogramming has been postulated to be one of the hallmarks of cancer, thus representing a promising therapeutic target also in glioblastoma multiforme (GBM). Hypoxic tumor cells produce lactate, and monocarboxylate transporters (MCTs) play an important role in its distribution; (2) Methods: We examined the distribution of lactate by multi voxel magnetic resonance spectroscopic imaging and ELISA in glioblastoma multiforme (GBM) patients. In addition, we investigated the expression and cellular localization of MCT1, MCT4, and of several markers connected to tumor progression by quantitative PCR and immunofluorescence double-staining in human GBM ex vivo tissues; (3) Results: The highest lactate concentration was found at the center of the vital parts of the tumor. Three main GBM groups could be distinguished according to their regional gene expression differences of the investigated genes. MCT1 and MCT4 were found on cells undergoing epithelial to mesenchymal transition and on tumor stem-like cells. GBM cells revealing an expression of cellular dormancy markers, showed positive staining for MCT4; (4) Conclusion: Our findings indicate the existence of individual differences in the regional distribution of MCT1 and MCT4 and suggest that both transporters have distinct connections to GBM progression processes, which could contribute to the drug resistance of MCT-inhibitors. View Full-Text
Keywords: glioblastoma; MCT1; MCT4; lactate; EMT; stemness; dormancy; MRSI glioblastoma; MCT1; MCT4; lactate; EMT; stemness; dormancy; MRSI
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Kubelt, C.; Peters, S.; Ahmeti, H.; Huhndorf, M.; Huber, L.; Cohrs, G.; Hövener, J.-B.; Jansen, O.; Synowitz, M.; Held-Feindt, J. Intratumoral Distribution of Lactate and the Monocarboxylate Transporters 1 and 4 in Human Glioblastoma Multiforme and Their Relationships to Tumor Progression-Associated Markers. Int. J. Mol. Sci. 2020, 21, 6254.

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