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https://hdl.handle.net/1822/67153
Título: | Monocarboxylate transporter 1 is a key player in glioma-endothelial cell crosstalk |
Autor(es): | Miranda-Gonçalves, Vera Bezerra, Filipa Costa-Almeida, Raquel Freitas-Cunha, Marta Soares, Raquel Martinho, Olga Reis, R. M. Pinheiro, Céline Baltazar, Fátima |
Palavras-chave: | Blotting, Western Brain Neoplasms Cell Line, Tumor Cell Movement Cell Proliferation Culture Media, Conditioned Endothelial Cells Glioma Humans Lactic Acid Monocarboxylic Acid Transporters Neovascularization, Pathologic RNA Interference Signal Transduction Symporters Tumor Microenvironment Angiogenesis Glioma cells Lactate |
Data: | Dez-2017 |
Editora: | Wiley |
Revista: | Molecular Carcinogenesis |
Citação: | Miranda‐Gonçalves, V., Bezerra, F., Costa‐Almeida, R., Freitas‐Cunha, M., et. al.(2017). Monocarboxylate transporter 1 is a key player in glioma‐endothelial cell crosstalk. Molecular Carcinogenesis, 56(12), 2630-2642 |
Resumo(s): | 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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/67153 |
DOI: | 10.1002/mc.22707 |
ISSN: | 0899-1987 |
e-ISSN: | 1098-2744 |
Versão da editora: | https://onlinelibrary.wiley.com/doi/full/10.1002/mc.22707 |
Arbitragem científica: | yes |
Acesso: | Acesso restrito UMinho |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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10.1002_mc.22707.pdf Acesso restrito! | 7,34 MB | Adobe PDF | Ver/Abrir |