Lactic Acid Found To Fuel Tumors

[epoh]

 

 

Source: http://www.sciencedaily.com/releases/2008/11/081120171325.htm

Lactic Acid Found To Fuel Tumors

 

ScienceDaily (Nov. 23, 2008)

? 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.

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, Communaut? fran?aise de Belgique

and R?gion 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 Universit? catholique de

Louvain (UCL), in Brussels, Belgium: Fr?d?rique V?gran, Julien Verrax,

and Christophe J. De Saedeleer from the Unit of Pharmacology &

Therapeutics; and Caroline Diepart, B?n?dicte F. Jordan, and Bernard

Gallez of the Unit of Biomedical Magnetic Resonance.

 

 

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Adapted from materials provided by Duke University Medical Center, via EurekAlert!, a service of AAAS.

 

[fandacious]

So if i grow a tumor it will burn my lactic... sounds good to me

[Mudsimus]

OT: Lactic acid has got nothing to do with cramps or muscle soreness. Its thanks to the production of lactate during exercise that you can keep going for so long. So apart from feeding the cancer, lactate is a good thing.

[fandacious]

yes, but lactic is what creates the "burn" when you reach your "lactic threshold". the lactic creates a burning sensation in your nerve endings and hence the pain.

 

so if i've got a tumour chowing the lactic i can go for longer

[Azonic]

I already got a tumour. It causes my leg muscles to be weak on climbs.

 

[fandacious]

interesting read on lactic

 

http://www.brianmac.co.uk/lactic.htm

[TheLegend]

 

OT: Lactic acid has got nothing to do with cramps or muscle soreness. Its thanks to the production of lactate during exercise that you can keep going for so long. So apart from feeding the cancer' date=' lactate is a good thing.

[/quote']

 

would you care to elaborate that a bit for the uninformed?

 

[Gravity Sucks]

Lactic acid does not cause the burn in your muscles but the by product of hydrogen ions which increase the acidity of your blood. Lactic acid is re cycled back into glycose for energy. Also been said lately that lactic acid is a free radical scavenger. So hence latate can be seen as a "friend"

[wpdeb]

I am sorry to disagree with you but lactic acid is not your friend - lactic acid is the by product of anaerobic metabolism, meaning that you go into oxygen debt.

Once you start building up lactic acid you will not be able to continue at the rate you are going and it will cause cramps and muscle pains.

Lactic acid build up is what's causing the muscle stiffness the day after.