ArticleNeuro-oncology2015
Melanoma brain metastasis is independent of lactate dehydrogenase A expression.
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Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Epithelial-to-mesenchymal transition (EMT) and cancer metastasis: the status quo of methods and experimental models 2025.Molecular cancer · 2025Review
- Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis.Neuro-oncology · 2024Article
- Itraconazole-Induced the Activation of Adenosine 5'-Monophosphate (Amp)-Activated Protein Kinase Inhibits Tumor Growth of Melanoma via Inhibiting ERK Signaling.Cell biochemistry and biophysics · 2022Article
- Cabozantinib Is Effective in Melanoma Brain Metastasis Cell Lines and Affects Key Signaling Pathways.International journal of molecular sciences · 2021Article
- Article
- Effective Treatment of Metastatic Melanoma by Combining MAPK and PI3K Signaling Pathway Inhibitors.International journal of molecular sciences · 2019Article
- Inhibition of mitochondrial respiration prevents BRAF-mutant melanoma brain metastasis.Acta neuropathologica communications · 2019Article
- Tyrosine Kinase Signaling in Cancer Metabolism: PKM2 Paradox in the Warburg Effect.Frontiers in cell and developmental biology · 2018Review
- Prognostic impact of lactic dehydrogenase to albumin ratio in hepatocellular carcinoma patients with Child-Pugh I who underwent curative resection: a prognostic nomogram study.Cancer management and research · 2018Article
- Current landscape and future perspectives in preclinical MR and PET imaging of brain metastasis.Neuro-oncology advancesReview
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Authors and funding
15 authors at 4 institutions in 3 countries.
Terje SundstrømDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Heidi EspedalDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Patrick N HarterDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Kristine Eldevik FasmerDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Kai Ove SkaftnesmoDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Sindre HornDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Erlend HodnelandDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Michel MittelbronnDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Benjamin WeideDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Rudi BeschornerDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Benjamin BenderDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Cecilie Brekke RyghDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Morten Lund-JohansenDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Rolf BjerkvigDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Frits ThorsenDepartment of Biomedicine, University of Bergen, Bergen, Norway (T.S., H.E., K.O.S., S.H., E.H., C.B.R., R.Bj., F.T.); Department of Clinical Medicine, University of Bergen, Bergen, Norway (T.S., M.L.-J.); Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (T.S., M.L.-J.); Edinger-Institute (Neurological Institute), Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H., M.M.); Center for Nuclear Medicine/PET, Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway (K.E.F.); Department of Dermatology, University Medical Center, Tübingen, Germany (B.W.); Department of Immunology, University of Tübingen, Tübingen, Germany (B.W.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.Be.); Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany (B.B.); NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (R.Bj.).
Haukeland University Hospital · NOUniversity of Tübingen · DELuxembourg Institute of Health · LUUniversity of Bergen · NO
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe key metabolic enzyme lactate dehydrogenase A (LDHA) is overexpressed in many cancers, and several preclinical studies have shown encouraging results of targeted inhibition. However, the mechanistic importance of LDHA in melanoma is largely unknown and hitherto unexplored in brain metastasis.
methodsWe investigated the spatial, temporal, and functional features of LDHA expression in melanoma brain metastasis across multiple in vitro assays, in a robust and predictive animal model employing MRI and PET imaging, and in a unique cohort of 80 operated patients. We further assessed the genomic and proteomic landscapes of LDHA in different cancers, particularly melanomas.
resultsLDHA expression was especially strong in early and small brain metastases in vivo and related to intratumoral hypoxia in late and large brain metastases in vivo and in patients. However, LDHA expression in human brain metastases was not associated with the number of tumors, BRAF(V600E) status, or survival. Moreover, LDHA depletion by small hairpin RNA interference did not affect cell proliferation or 3D tumorsphere growth in vitro or brain metastasis formation or survival in vivo. Integrated analyses of the genomic and proteomic landscapes of LDHA indicated that LDHA is present but not imperative for tumor progression within the CNS, or predictive of survival in melanoma patients.
conclusionsIn a large patient cohort and in a robust animal model, we show that although LDHA expression varies biphasically during melanoma brain metastasis formation, tumor progression and survival seem to be functionally independent of LDHA.
Indexed as
AnimalsBrain NeoplasmsCell HypoxiaCell Line, TumorFemaleGene Knockdown TechniquesHumansIsoenzymesLactate Dehydrogenase 5L-Lactate DehydrogenaseMelanomaMiceSurvival AnalysisIsoenzymesLactate Dehydrogenase 5L-Lactate Dehydrogenasebrain metastasislactate dehydrogenase ALDHAmelanomametabolism
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