Melanoma brain metastasis is independent of lactate dehydrogenase A expression

Neuro-oncology
Terje SundstrømFrits Thorsen

Abstract

The 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. We 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. LDHA 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...Continue Reading

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Citations

Sep 1, 2019·International Journal of Molecular Sciences·Synnøve Nymark AasenFrits Thorsen
Apr 12, 2019·Acta Neuropathologica Communications·Terje SundstrømFrits Thorsen
Jan 26, 2016·Current Opinion in Oncology·Simone M GoldingerPaul Nathan
Aug 9, 2018·Frontiers in Cell and Developmental Biology·Elizabeth K Wiese, Taro Hitosugi

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