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Premium Monocarboxylate transporter 1 is a key player in glioma‐endothelial cell crosstalk
MirandaGonçalves Vera,
Bezerra Filipa,
CostaAlmeida Raquel,
FreitasCunha Marta,
Soares Raquel,
Martinho Olga,
Reis Rui M.,
Pinheiro Céline,
Baltazar Fátima
Publication year2017
Publication title
molecular carcinogenesis
Resource typeJournals
Glioblastoma (GBM) is one of the most glycolytic and angiogenic human tumors, characteristics that contribute to the poor prognosis associated with this type of tumor. A lactate shuttle has been described between tumor cells and endothelial cells (ECs), with the monocarboxylate transporters (MCTs) acting as important players in this tumor‐EC communication. In this study, we aimed to understand how the tumor microenvironment modulates EC metabolism, and to characterize the role of MCTs in the glioma‐brain EC crosstalk. Exposure of human brain microvascular ECs (HBMEC) to GBM cell‐conditioned media increased the expression of MCT1, which corresponded to activation of oxidative metabolism and an increase in angiogenic capacity, as determined by increased proliferation, migration, and vessel assembly. Lactate depletion from the microenvironment or inhibition of lactate uptake in HBMEC induced an increase in lactate production and a decrease in proliferation, migration, and vessel assembly. Moreover, addition of lactate to HBMEC media promoted activation of AKT and AMPK pathways and increased expression in NFκB, HIF‐1α, and the lactate receptor GPR81. Here, we demonstrate a role for MCT1 as a mediator of lactate signaling between glioma cells and brain ECs. Our results suggest that MCT1 can mediate EC metabolic reprograming, proliferation, and vessel sprouting in response to tumor signaling. Thus, targeting MCT1 in both tumor cells and brain EC may be a promising therapeutic strategy for the treatment of GBM.
Subject(s)ampk , biology , cancer research , crosstalk , endocrinology , glioma , glucose transporter , glycolysis , insulin , metabolism , microbiology and biotechnology , optics , phosphorylation , physics , protein kinase a , tumor cells , tumor microenvironment
SCImago Journal Rank1.254

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