Lactic acid found to fuel tumors (overed that a transporter protein of mus...)

Lactic acid found to fuel tumors

Date:11/20/2008

overed 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."

Even though hypoxic tumor cells have been identified as a cause of treatment resistance for decades, there has not been a reliable method to kill them. "They are the population of cells that can cause tumor relapse," said Professor Feron.

A significant advantage of the new strategy is that a new drug does not need to reach hypoxic cells far from blood vessels and it does not need to enter into cells at all it merely needs to block the transporter molecule that moves the lactose, which is outside of the cells. "This finding will be really important for drug development," said Sonveaux.

The researchers also showed in mice that radiation therapy along with MCT1 inhibition was effective for killing the remaining tumor cells, those nearest the blood vessels. This proved to be a substantial antitumor approach.

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Contact: Mary Jane Gore
mary.gore@duke.edu
919-323-0179
Duke University Medical Center
Source:Eurekalert

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