title: The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism.
abstract: 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.
authors.affiliation: CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Vanessa R
authors.initials: VR
authors.lastname: Conde
authors.affiliation: CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal; Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto - UMIB/ICBAS/UP, Portugal.
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Oliveira
authors.affiliation: CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Nunes
authors.affiliation: CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Cátia S
authors.initials: CS
authors.lastname: Rocha
authors.affiliation: Mountain Research Centre (CIMO), School of Agriculture, Polytechnic Institute of Bragança, Portugal.
authors.forename: Elsa
authors.initials: E
authors.lastname: Ramalhosa
authors.affiliation: Mountain Research Centre (CIMO), School of Agriculture, Polytechnic Institute of Bragança, Portugal.
authors.forename: José A
authors.initials: JA
authors.lastname: Pereira
authors.affiliation: CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal. Electronic address: alvesmarc@gmail.com.
authors.forename: Marco G
authors.initials: MG
authors.lastname: Alves
authors.affiliation: CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal. Electronic address: bmcms@ubi.pt.
authors.forename: Branca M
authors.initials: BM
authors.lastname: Silva
mesh_terms: D000409:Alanine / Q000378:metabolism; D000410:Alanine Transaminase / Q000096:biosynthesis; D045744:Cell Line, Tumor; D018450:Disease Progression; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis; D051274:Glucose Transporter Type 3 / Q000096:biosynthesis; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D019344:Lactic Acid / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000096:biosynthesis; D009124:Muscle Proteins / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010732:Phosphofructokinase-1 / Q000096:biosynthesis; D019289:Pyruvic Acid / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; C406962:SLC16A4 protein, human; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; D019344:Lactic Acid; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D010732:Phosphofructokinase-1; D005947:Glucose; D000409:Alanine
keywords: Bladder cancer; Metabolism; RT4; TCCSUP; Warburg effect