Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth.

Abstract

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.

• Authors: 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
• Journal: eLife (Elife) Vol. 9 (06 23 2020) ISSN: 2050-084X [Electronic] England
• PMID: 32571479 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020, Contat et al.

Chemical References

• Glucose Transporter Type 1
• Glucose Transporter Type 2
• SLC2A1 protein, human
• SLC2A2 protein, human
• Slc2a1 protein, mouse
• Slc2a2 protein, mouse
• Fluorodeoxyglucose F18
• Glucose

Topics

• Adenocarcinoma of Lung (physiopathology)
• Animals
• Cell Line, Tumor
• Female
• Fluorodeoxyglucose F18 (chemistry)
• Gene Deletion
• Glucose (metabolism)
• Glucose Transporter Type 1 (genetics, metabolism)
• Glucose Transporter Type 2 (genetics, metabolism)
• Humans
• Male
• Mice
• Mice, Transgenic
• Microscopy, Electron, Scanning
• Microscopy, Electron, Transmission
• Positron-Emission Tomography
• Spectrometry, Mass, Secondary Ion