Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells

F. Lopes-Coelho, C. Nunes, S. Gouveia-Fernandes, Rita Rosas, F. Silva, P. Gameiro, T. Carvalho, M.G. da Silva, J. Cabeçadas, S. Dias, L.G. Gonçalves, J. Serpa

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Abstract

Dysregulation of glucose/lactate dynamics plays a role in cancer progression, and MCTs are key elements in metabolic remodeling. VEGF is a relevant growth factor in the maintenance of bone marrow microenvironment and it is also important in hematological diseases. Our aim was to investigate the role of VEGF in the metabolic adaptation of Acute myeloid leukemia (AML) cells by evaluating the metabolic profiles and cell features according to the AML lineage and testing lactate as a metabolic coin. Our in vitro results showed that AML promyelocytic (HL60) and monocytic (THP1) (but not erythroid- HEL) lineages are well adapted to VEGF and lactate rich environment. Their metabolic adaptation relies on high rates of glycolysis to generate intermediates for PPP to support cell proliferation, and on the consumption of glycolysis-generated lactate to supply biomass and energy production. VEGF orchestrates this metabolic network by regulating MCT1 expression. Bromopyruvic acid (BPA) was proven to be an effective cytotoxic in AML, possibly transported by MCT1. Our study reinforces that targeting metabolism can be a good strategy to fight cancer. MCT1 expression at the time of diagnosis can assist on the identification of AML patients that will benefit from BPA therapy. Additionally, MCT1 can be used in targeted delivery of conventional cytotoxic drugs. © Lopes-Coelho et al.
Original languageEnglish
Pages (from-to)82803-82823
Number of pages21
JournalOncotarget
Volume8
Issue number47
DOIs
Publication statusPublished - 2017

Keywords

  • BM microenvironment
  • Lactate
  • MCT1
  • Metabolic switch
  • VEGF

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