Cancer cells are well known for their altered metabolisms, which may help them generate the energy they need for rapid growth. Using an emerging imaging technology, researchers reporting in the July Cell Metabolism, a Cell Press publication, have discovered that those metabolic shifts actually develop even before detectable tumors form. By the same token, the studies in mice with liver cancer show that the altered tumor metabolism shifts back before established tumors shrink.
"This may be an early diagnostic in liver cancer and a way to assess tumor response to treatment," said Andrei Goga of the University of California, San Francisco.
The increased conversion of glucose into lactate had been observed in tumor cells in culture before, Goga explained. But there hadn't been a good way to see those dynamic changes in glycolysis (the metabolic pathway that converts glucose into pyruvate to release energy) in a living animal.
His team sought to change that using hyperpolarized 13C-pyruvate magnetic resonance spectroscopic imaging (MRSI) in mice whose cancer could be turned on and off via a single cancer-causing oncogene known as Myc. The imaging method made it possible to see the real-time conversion of pyruvate, a key product of glycolysis, into other metabolites as tumors began to grow and then to shrink.
"The model allowed us to see what happens before a tumor forms," Goga said.
What they saw was that the conversion of pyruvate to lactate increased as tumors developed, with the conversion of pyruvate into alanine predominating very early in precancerous tissues.
"We were surprised to see that very early shift," he said. They aren't yet sure exactly what it means, but Goga suggests it may lead to new strategies to tackle cancer in those earliest stages.
When the oncogene was switched off in mice with liver tumors, changes in metabolism were apparent three days later. "The metabolism falls
|Contact: Elisabeth Lyons|