Metabolic

Blocking the sugar metabolism slows the expansion of lung most cancers tumors

Photo credit: EPFL

Treatments that block two sugar-transporting proteins could slow lung tumor growth, new research from EPFL suggests.

Blocking a pair of sugar transporting proteins could be a useful approach to treatment for lung cancer, suggests a new study in mice and human cells published in eLife today.

Cancer cells consume a lot of sugar to promote their rapid growth and spread. This has led scientists to consider cutting off sugar supplies to treat cancer. The current study suggests that this could be an effective approach, but it will be necessary to block multiple avenues at once in order to be effective.

Proteins, so-called glucose transporters, supply the cells with sugar, which makes them an attractive target for therapies aimed at starving cancer cells. However, scientists don’t know how this works best or whether cancer cells would simply switch to alternative fuel sources if they were denied sugar.

“Inhibiting sugar consumption in lung tumors could be an efficient treatment strategy, but whether glucose transporters should be used specifically and which ones should be used remains unclear,” says lead author Caroline Contat, doctoral student at the Swiss Institute for Experimental Cancer Research, EPFL, Lausanne , Switzerland.

To find out, Contat and her colleagues genetically engineered mice with lung cancer that lacked a glucose transport protein called Glut1 or an alternative sugar transporter called Glut3. The team found that tumors in mice without Glut1 or Glut3 grew just as quickly as in mice with both transporters.

However, when they genetically engineered mice with lung cancer that lacked both Glut1 and Glut3, they found that the animals grew fewer tumors and survived longer. By using an imaging technology called positron emission tomography (PET) and sugar labeled with radiolabels, the team confirmed that the tumors used less sugar. The tumor cells also grew more slowly.

Eventually, they deleted Glut1 and Glut3 in four different human lung cancer cell lines that were grown in the laboratory, which made these cells grow more slowly. “These experiments suggest that Glut1 and Glut3 are needed together to promote lung cancer growth,” says Contat.

Using nanoscale imaging, the team also found that most of the sugar-derived biomass in mouse lung tumor cells accumulates in cell compartments called lamellar bodies, and that Glut1 is required for this fuel storage.

“Although more studies of these tumor fuel storage compartments are needed, our results suggest a new approach to lung cancer treatment that focuses on starving tumor cells with energy,” says senior author Etienne Meylan, assistant professor at the Swiss Institute for Experimental Cancer research. EPFL. “In particular, treatments that block Glut1 and Glut3 at the same time will be needed to stop lung tumor growth.”

Reference: “The combined deletion of Glut1 and Glut3 impairs the growth of lung adenocarcinomas” by 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 and Etienne Meylan, June 23, 2020, eLife.
DOI: 10.7554 / eLife.53618

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