Belgian researchers have discovered that some cancer cells use lactic acid instead of sugar for food, and this might lead to new treatments that starve and kill these cells.
To survive and proliferate, all cells in the body need to produce energy. They do this by burning sugar (glucose), a process that requires oxygen. Compared with normal cells, tumor cells have restricted access to oxygen. Some tumor cells become starved for oxygen (hypoxic) and produce lactic acid. Until now, it was believed that both types of tumor cells used glucose as their main fuel, the study authors said.
"Using models of tumor cells, we found that well-oxygenated cells use lactate (lactic acid) as a preferential substrate to produce energy," said lead researcher Pierre Sonveaux, an associate professor at the University of Louvain Medical School in Brussels.
In other words, when these oxygenated cells choose between glucose and lactic acid, they choose lactic acid, Sonveaux explained. "The well-oxygenated cells thus recycle the waste product of hypoxic cells," he said.
The researchers identified the gate through which lactic acid enters oxygenated cells -- a transporter protein called MCT1 (monocarboxylate transporter 1). "The same transporter is present in the muscle where it helps to clear lactate to prevent cramps," Sonveaux said.
Tumors are famous for co-opting normal body functions, Sonveaux said. "What we identified is thus another example of usurpation by tumor cells of a normal system diverted to promote tumor growth," he said.
In experiments with mice with tumors, Sonveaux's group used a drug to block MCT1, preventing the oxygenated cells from using lactic acid as an energy source. These cells survived by switching to glucose, and they also stopped using oxygen.
This resulted in the death of hypoxic tumor cells. "Oxygenated cells close to blood vessels used glucose so abundantly that the hypoxic cells far from the blood vessels died from glucose starvation," Sonveaux said.
Sonveaux noted that hypoxic cells are particularly resistant to all forms of anticancer therapies, including chemotherapy and radiotherapy. But after blocking MCT1, radiation killed most of the cancerous cells, he said.
Tumor cells cooperate to produce energy, Sonveaux said. "This cooperation can be corrupted therapeutically to destroy the most hard-to-kill cancer cells. This approach is unique and has the potential to cure cancer in combination with radiotherapy. It has also the potential to be applicable to a wide range of human tumors, after the development of a drug compatible with human use," he said.
Drugs that block MCT1 are in development, but clinical trials using this approach are at least several years away, Sonveaux said.
Illustration: Microsoft clipart.
US News & World Report (11/21/08)
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Abstract (Journal of Clinical Investigation; 118(12), 3930-3942 (12/01/08))