Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth
Caroline Contat,
Pierre-Benoit Ancey,
Nadine Zangger,
Silvia Sabatino,
Justine Pascual,
Stéphane Escrig,
Louise Jensen,
Christine Goepfert,
Bernard Lanz,
Mario Lepore,
Rolf Gruetter,
Anouk Rossier,
Sabina Berezowska,
Christina Neppl,
Inti Zlobec,
Stéphanie Clerc-Rosset,
Graham William Knott,
Jeffrey C Rathmell,
E Dale Abel,
Anders Meibom,
Etienne Meylan
Affiliations
Caroline Contat
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Cancer Center Léman, Lausanne, Switzerland
Pierre-Benoit Ancey
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Cancer Center Léman, Lausanne, Switzerland
Nadine Zangger
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Cancer Center Léman, Lausanne, Switzerland; Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne, Switzerland
Silvia Sabatino
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Cancer Center Léman, Lausanne, Switzerland
Justine Pascual
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Cancer Center Léman, Lausanne, Switzerland
Stéphane Escrig
Laboratory for Biological Geochemistry, School of Architecture, Civil and Environmental Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Louise Jensen
Laboratory for Biological Geochemistry, School of Architecture, Civil and Environmental Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Christine Goepfert
Institute of Animal Pathology (COMPATH), University of Bern, CH-3012 Bern, and Histology Core Facility, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Bernard Lanz
Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Mario Lepore
Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Rolf Gruetter
Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Anouk Rossier
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Cancer Center Léman, Lausanne, Switzerland
Sabina Berezowska
Institute of Pathology, University of Bern, Bern, Switzerland
Christina Neppl
Institute of Pathology, University of Bern, Bern, Switzerland
Inti Zlobec
Institute of Pathology, University of Bern, Bern, Switzerland
Stéphanie Clerc-Rosset
BioEM Facility, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, United States
Anders Meibom
Laboratory for Biological Geochemistry, School of Architecture, Civil and Environmental Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Center for Advanced Surface Analysis, Faculty of Geosciences and Environment, University of Lausanne, Lausanne, Switzerland
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Cancer Center Léman, Lausanne, Switzerland
Glucose utilization increases in tumors, a metabolic process that is observed clinically by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). However, is increased glucose uptake important for tumor cells, and which transporters are implicated in vivo? In a genetically-engineered mouse model of lung adenocarcinoma, we show that the deletion of only one highly expressed glucose transporter, Glut1 or Glut3, in cancer cells does not impair tumor growth, whereas their combined loss diminishes tumor development. 18F-FDG-PET analyses of tumors demonstrate that Glut1 and Glut3 loss decreases glucose uptake, which is mainly dependent on Glut1. Using 13C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we also report the presence of lamellar body-like organelles in tumor cells accumulating glucose-derived biomass, depending partially on Glut1. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma, the dual blockade of which could reach therapeutic responses not achieved by individual targeting.
