Featured Research

from universities, journals, and other organizations

Lactic Acid Found To Fuel Tumors

Date:
November 23, 2008
Source:
Duke University Medical Center
Summary:
A team of researchers 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.

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.

Related Articles


"We have known for more than 50 years that low-oxygen, or hypoxic, cells cause resistance to radiation therapy," said senior co-author Mark Dewhirst, DVM, Ph.D., professor of radiation oncology and pathology at Duke. "Over the past 10 years, scientists have found that hypoxic cells are also more aggressive and hard to treat with chemotherapy. The work we have done presents an entirely new way for us to go after them."

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. He formerly worked with Dr. Dewhirst at Duke.

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."

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.

The study was funded by grants from the National Institutes of Health; the Belgian American Educational Foundation (BAEF); from governmental foundations, F.R.S.-FNRS, Communauté française de Belgique and Région wallonne; and the J. Maisin and St. Luc Foundations in Belgium.

Other authors included, from Duke University Medical Center: Thies Schroeder, Melanie C. Wergin, Zahid N. Rabbani, and Kelly M. Kennedy from the Department of Radiation Oncology; Michael J. Kelley, from the Division of Hematology and Medical Oncology; and Miriam L. Wahl from the Department of Pathology. And from the Université catholique de Louvain (UCL), in Brussels, Belgium: Frédérique Végran, Julien Verrax, and Christophe J. De Saedeleer from the Unit of Pharmacology & Therapeutics; and Caroline Diepart, Bénédicte F. Jordan, and Bernard Gallez of the Unit of Biomedical Magnetic Resonance.


Story Source:

The above story is based on materials provided by Duke University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Duke University Medical Center. "Lactic Acid Found To Fuel Tumors." ScienceDaily. ScienceDaily, 23 November 2008. <www.sciencedaily.com/releases/2008/11/081120171325.htm>.
Duke University Medical Center. (2008, November 23). Lactic Acid Found To Fuel Tumors. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2008/11/081120171325.htm
Duke University Medical Center. "Lactic Acid Found To Fuel Tumors." ScienceDaily. www.sciencedaily.com/releases/2008/11/081120171325.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) — A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) — Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Reuters - Innovations Video Online (Dec. 21, 2014) — A team of scientists led by Danish chemist Jorn Christensen says they have isolated two chemical compounds within an existing antipsychotic medication that could be used to help a range of failing antibiotics work against killer bacterial infections, such as Tuberculosis. Jim Drury went to meet him. Video provided by Reuters
Powered by NewsLook.com
Hugging It Out Could Help You Ward Off A Cold

Hugging It Out Could Help You Ward Off A Cold

Newsy (Dec. 21, 2014) — Carnegie Mellon researchers found frequent hugs can help people avoid stress-related illnesses. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins