Blocking a pair of sugar-transporting proteins may be a useful
treatment approach for lung cancer, suggests a new study in mice and
human cells published today in
eLife.
Cancer cells use a lot of sugar to fuel their rapid growth and
spread. This has led scientists to consider cutting off their sugar
supply as a way to treat cancer. The current study suggests this could
be an effective approach but it will be necessary to block multiple
pathways at once to be effective.
Proteins called glucose transporters supply sugar to cells making
them an appealing target for therapies intended to starve cancer cells.
But scientists don’t know the best ways to do this, or if cancer cells
would just switch to alternative fuel sources if they are denied sugar.
“Inhibiting sugar use in lung tumours could be an efficient treatment
strategy, but whether glucose transporters should be targeted and which
ones to target remains unclear,” says lead author Caroline Contat, a
PhD student and Doctoral Assistant 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 were missing a glucose transport protein called
Glut1 or an alternate sugar transporter called Glut3. The team found
that tumours grew just as fast in the mice lacking Glut1 or Glut3 as
they did in mice with both transporters.
However, when they genetically engineered mice with lung cancer that
lack both Glut1 and Glut3, they found that the animals grew fewer
tumours and survived longer. By using an imaging technology called
positron emission tomography (PET) and sugar labelled with radioactive
tags, the team confirmed that the tumours used less sugar. The tumour
cells also grew more slowly.
Finally, they deleted Glut1 and Glut3 in four different human lung
cancer cell lines grown in the laboratory, which caused these cells to
grow more slowly. “These experiments suggest Glut1 and Glut3 together
are needed to fuel the growth of lung cancer,” Contat says.
Using nanoscale imaging studies, the team also found that most of the
sugar-derived biomass in mouse lung tumour cells accumulates in
cellular compartments called lamellar bodies and that Glut1 is necessary
for this fuel storage.
“While more studies of these tumour fuel storage compartments are
needed, our results suggest a new approach to lung cancer treatment that
focuses on starving tumour cells of 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 simultaneously will be necessary to help stop lung tumour growth.”
###
Reference
The paper ‘Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth’ can be freely accessed online at
https://doi.org/10.7554/eLife.53618. Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.
https://www.eurekalert.org/pub_releases/2020-06/e-bsm062320.php
