Navigation Links
Lactic acid found to fuel tumors
Date:11/20/2008

DURHAM, N.C., and BRUSSELS, BELGIUM A team of researchers at Duke University Medical Center and the Universit 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.

"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.


'/>"/>

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

Related medicine news :

1. Prophylactic cranial irradiation in small cell lung cancer significantly increases survival
2. One Species Genome Found Within Another
3. National Patient Safety Foundation Partners with Vocera Communications
4. R. P. Simmons Family Foundation Pledges $2 Million for New Childrens Hospital of Pittsburgh of UPMC Campus
5. Patient Advocate Foundation Launches Program to Help Uninsured Virginians with Chronic, Debilitating and Life-Threatening Illness Access Quality Healthcare
6. AIDS Healthcare Foundation Applauds City Commissioners Support of Diversity, Urges Call for Mayors Resignation
7. National Osteoporosis Foundation Teams Up With Ladies Home Journal Magazine to Launch a 10-city Mall Walk Tour
8. Judge Rules That Florida Disease Management Program Serving 8,000 HIV/AIDS Patients Should Be Re-bid, Says AIDS Healthcare Foundation
9. The Tug McGraw Foundation Announces 2007 Fundraising Gala
10. The Arthur M. Blank Family Foundation Pushes for Pre-K Expansion in Georgia
11. Cipla, Tell the Truth; AIDS Healthcare Foundation Launches New Ad Campaign
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/25/2017)... ... ... Swissray is pleased to announce the release of the ELITE DXA, a new bone ... scan window, which is more than double that of existing bone densitometers. Historically, subjects ... an accurate total body bone density or body composition study. The ELITE DXA ...
(Date:3/24/2017)... ... March 24, 2017 , ... Vighter established its NAEMT ... by providing Prehospital Trauma Life Support (PHTLS) course scholarships to four medics assigned ... education developed in cooperation with the American College of Surgeons to promote critical ...
(Date:3/24/2017)... NY (PRWEB) , ... March 24, 2017 , ... ... scale; from third world countries to hospitals in the United States, it’s a ... conversation on the current obstacles facing infection prevention and offers strategies for the ...
(Date:3/24/2017)... ... March 24, 2017 , ... The Radiology Business Management Association (RBMA) ... awards, now in their 12th year, are among the most prestigious in radiology marketing ... the awards were retooled to recognize achievements in both large budget (over $5,000) and ...
(Date:3/24/2017)... TX (PRWEB) , ... March 24, 2017 , ... ... clinic which can be found at 9618 Huebner Road. The clinic is the group’s ... OCS, Clinic Director, and Dr. Ali Higgins, PT, will provide care from the clinic, ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... DUBLIN , Mar 24, 2017 Research ... in Drug Discovery and Diagnostics, 2017 - 2035" report to ... The ... current landscape and future outlook of the growing market of deep ... data revolution, deep learning algorithms have emerged as a novel solution ...
(Date:3/24/2017)... 24, 2017 Today Stock-Callers.com have issued ... are: Neovasc Inc. (NASDAQ: NVCN), Hologic Inc. (NASDAQ: HOLX), Edwards ... SSH ). These companies are part of the Healthcare ... Thursday, March 23 rd , 2017, with the NYSE Health ... health care companies in the S&P 500 were down about ...
(Date:3/24/2017)... INDIANAPOLIS , March 24, 2017  Eli ... today announced plans to invest $850 million in ... span facilities across its U.S. enterprise, including research ... The investments are being driven by demand for ... of potential medicines in development targeting cancer, pain, ...
Breaking Medicine Technology: