Metabolic alterations associated with bladder cancer progression were unveiled

A group of researchers from the Faculty of Health Sciences, University of Beira Interior (UBI-FCS), of the Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP) and of the School of Agriculture, Polytechnic Institute of Bragança (IPB) reported that the progression of bladder cancer from a less invasive stage to a highly invasive stage is accompanied by alterations in the metabolic phenotype of tumor cells. Since decades it is recognized that tumor cells have very specific metabolic properties associated with the malignant behavior of these cells. The research carried out in cell lines and led by Branca Silva, Associate Professor at UBI, showed that bladder cancer progression is associated with a switch from glucose consumption, usually reported as the essential substrate, to pyruvate consumption. Since several therapies are proposed based on specific phenotype characteristics of tumor cells, this discovery can allow to identify biomarkers for bladder cancer progression and also to develop new effective therapies.

Authors and Affiliations:

Vanessa R. Conde1, Pedro F. Oliveira1,2, Ana R. Nunes1, Cátia S. Rocha1, Elsa Ramalhosa3, José A. Pereira3, Marco G. Alves1, Branca M. Silva1

¹- CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal

²- 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

³- Mountain Research Centre (CIMO), School of Agriculture, Polytechnic Institute of Bragança, Portugal

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.

Journal: Experimental Cell Research

Link: http://www.sciencedirect.com/science/article/pii/S001448271500141X