Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells
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Filipa Lopes-Coelho1,2, Carolina Nunes1,2, Sofia Gouveia-Fernandes1,2, Rita Rosas3, Fernanda Silva1,2, Paula Gameiro4, Tânia Carvalho5, Maria Gomes da Silva4, José Cabeçadas6, Sérgio Dias5, Luís G. Gonçalves3 and Jacinta Serpa1,2
1Centro de Estudos de Doenças Crónicas da Faculdade de Ciências Médicas da Universidade NOVA (CEDOC-FCM-UNL), Lisbon, Portugal
2Unidade de Investigação em Patobiologia Molecular do Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Lisbon, Portugal
3Instituto de Tecnologia Química e Biológica António Xavier (ITQB Nova), Oeiras, Portugal
4Serviço de Hemato-Oncologia, IPOLFG, Lisbon, Portugal
5Instituto de Medicina Molecular da Universidade de Lisboa, Lisbon, Portugal
6Serviço de Anatomia Patológica, IPOLFG, Lisbon, Portugal
Jacinta Serpa, email: [email protected]
Keywords: metabolic switch, MCT1, lactate, VEGF, BM microenvironment
Received: February 08, 2017 Accepted: June 27, 2017 Published: August 16, 2017
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.
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