Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile |
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| Authors: | Cátia V Vaz Marco G Alves Ricardo Marques Paula I Moreira Pedro F Oliveira Cláudio J Maia Sílvia Socorro |
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| Institution: | 1. CICS-UBI – Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal;2. CNC – Center for Neuroscience and Cell Biology and Institute of Physiology, Faculty of Medicine, University of Coimbra, 3004-517 Coimbra, Portugal;1. CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal;2. IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal;3. Department of Veterinary Sciences, Animal and Veterinary Science Research Center (CECAV), University of Trás-os-Montes and Alto Douro (UTAD), Portugal;4. Medical Faculty, University of Porto, Porto, Portugal;5. Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Canada;6. Department of Pathology, University Health Network, Toronto, Canada;3. From the Departments of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio 44106;4. Molecular Biology, Scripps Research Institute, La Jolla, California 92037;1. CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal;2. Centre for Reproductive Genetics Alberto Barros, 4100-009 Porto, Portugal;3. Department of Genetics, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal;4. Department of Microscopy, Laboratory of Cell Biology and Biomedical Research Multidisciplinary Unit (UMIB-FCT), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4099-003 Porto, Portugal;1. CICS – UBI – Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal;2. Department of Microscopy, Laboratory of Cell Biology & Multidisciplinary Unit for Biomedical Research, UMIB-FCT, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Portugal;3. Centre for Reproductive Genetics Alberto Barros, Porto, Portugal |
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| Abstract: | Prostate cancer (PCa) progresses from an early stage, confined to prostate, to a more aggressive metastasized cancer related with loss of androgen responsiveness. Although, it has been recognized that PCa cells have unique metabolic features, their glycolytic profile in androgen-dependent and androgen-independent stages of disease is much less known. Hence, the main purpose of this study was to compare glucose metabolism in androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) PCa cells. Cell culture medium was collected and differences in glucose consumption and, lactate and alanine production were measured using Proton Nuclear Magnetic Resonance ((1)H NMR) spectra analysis. The mRNA and protein expression of glucose transporters (GLUT1 and GLUT3), phosphofructokinase 1 (PFK1), lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT4) were determined by real-time PCR and Western Blot, respectively. The obtained results demonstrate that androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) cells consumed similar amounts of glucose, whereas PC3 cells present higher lactate production. This increase in lactate production was concomitant with higher levels of MCT4 protein, increased LDH activity and higher lactate/alanine ratio, also suggesting increased levels of oxidative stress in PC3 cells. However, protein levels of LDH, associated with lactate metabolism, and GLUT3, involved in glucose uptake, were decreased in PC3 comparatively with LNCaP. Androgen-responsive and nonresponsive PCa cells present distinct glycolytic metabolism profiles, which suggest that targeting LDH and MCT4 metabolic pathways may be an important step for the development of new diagnostic and therapeutic strategies in the different stages of PCa. |
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