4.6 Article

The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

Journal

EXPERIMENTAL CELL RESEARCH
Volume 335, Issue 1, Pages 91-98

Publisher

ELSEVIER INC
DOI: 10.1016/j.yexcr.2015.04.007

Keywords

Bladder cancer; TCCSUP; RT4; Metabolism; Warburg effect

Funding

  1. Fundacao para a Ciencia e a Tecnologia-FCT [PTDC/QUI-BIQ/121446/2010, PEst-C/SAU/UI0709/2014]
  2. Fundo Europeu de Desenvolvimento Regional - FEDER via Programa Operacional Factores de Competitividade - COMPETE/QREN [0671_RED_AGROTEC_6_E]
  3. FCT [SFRH/BPD/80451/2011]
  4. FCT through FSE
  5. POPH funds
  6. Fundação para a Ciência e a Tecnologia [PEst-OE/SAU/UI0709/2014, PTDC/QUI-BIQ/121446/2010] Funding Source: FCT

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Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similar in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. (C) 2015 Elsevier Inc. All rights reserved.

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