A story that merits close attention: both for how the research will be reported in tomorrow’s newspapers, and how the scientific community reacts.
A team of researchers at Duke University Medical Center and the Université catholique de Louvain (UCL) has found that lactic acid is an important energy source for tumor cells. In further experiments, they discovered a new way to destroy the most hard-to-kill, dangerous tumor cells by preventing them from delivering lactic acid.
…
Many tumors have cells that burn fuel for activities in different ways. Tumor cells near blood vessels have adequate oxygen sources and can either burn glucose like normal cells, or lactic acid (lactate). Tumor cells further from vessels are hypoxic and inefficiently burn a lot of glucose to keep going. In turn, they produce lactate as a waste product.
Tumor cells with good oxygen supply actually prefer to burn lactate, which frees up glucose to be used by the less-oxygenated cells. But when the researchers cut off the cells’ ability to use lactate, the hypoxic cells didn’t get as much glucose.
For the dangerous hypoxic cells, “it is glucose or death,” said Pierre Sonveaux, professor in the UCL Unit of Pharmacology & Therapeutics and lead author of the study, published in the Nov. 20 online edition of the Journal of Clinical Investigation. ….
The next challenge was to discover how lactate moved into tumor cells. Because lactate recycling exists in exercising muscle to prevent cramps, the researchers imagined that the same molecular machinery could be used by tumor cells. “We discovered that a transporter protein of muscle origin, MCT1, was also present in respiring tumor cells,” said Dewhirst. The team used chemical inhibitors of MCT1 and cell models in which MCT1 had been deleted to learn its role in delivering lactate. “We not only proved that MCT1 was important, we formally demonstrated that MCT1 was unique for mediating lactate uptake,” said Professor Olivier Feron of the UCL Unit of Pharmacology & Therapeutics.
Blocking MCT1 did not kill the oxygenated cells, but it nudged their metabolism toward inefficiently burning glucose. Because the glucose was used more abundantly by the better-oxygenated cells, they used up most of the glucose before it could reach the hypoxic cells, which starved while waiting in vain for glucose to arrive. “This finding is really exciting,” Dewhirst said. “The idea of starving hypoxic cells to death is completely novel.”
[Continue reading: Lactic Acid Found To Fuel Tumors]
Very interesting stuff.