Glutamine ratio is key ovarian cancer indicator

A Rice University-led analysis of the metabolic profiles of hundreds of ovarian tumors has revealed a new test to determine whether ovarian cancer cells have the potential to metastasize, or spread to other parts of the body. The study also suggests how ovarian cancer treatments can be tailored based on the metabolic profile of a particular tumor.

The research, which appears online this week in Molecular Systems Biology, was conducted at the Texas Medical Center in Houston by researchers from Rice, the University of Texas MD Anderson Cancer Center and Baylor College of Medicine.

"We found a striking difference between the metabolic profiles of poorly aggressive and highly aggressive ovarian tumor cells, particularly with respect to their production and use of the amino acid glutamine," said lead researcher Deepak Nagrath of Rice. "For example, we found that highly aggressive ovarian cancer cells are glutamine-dependent, and in our laboratory studies, we showed that depriving such cells of external sources of glutamine - as some experimental drugs do - was an effective way to kill late-stage cells.

"The story for poorly aggressive cells was quite different," said Nagrath, assistant professor of chemical and biomolecular engineering and of bioengineering at Rice. "These cells use an internal metabolic pathway to produce a significant portion of the glutamine that they consume, so a different type of treatment - one aimed toward internal glutamine sources - will be needed to target cells of this type."

The research is part of a growing effort among cancer researchers worldwide to create treatments that target the altered metabolism of cancer cells. It has long been known that cancer cells adjust their metabolism in subtle ways that allow them to proliferate faster and survive better. In 1924, Otto Warburg showed that cancer cells produced far more energy from glycolysis than did normal cells. The Nobel Prize-winning discovery became known as the "Warburg effect," and researchers long believed that all cancers behaved in this way. Intense research in recent decades has revealed a more nuanced picture.

"Each type of cancer appears to have its own metabolic signature," Nagrath said. "For instance, kidney cancer does not rely on glutamine, and though breast cancer gets some of its energy from glutamine, it gets even more from glycolysis. For other cancers, including glioblastoma and pancreatic cancer, glutamine appears to be the primary energy source."

Nagrath, director of Rice's Laboratory for Systems Biology of Human Diseases, said the new metabolic analysis indicates that ovarian cancer may be susceptible to multidrug cocktails, particularly if the amounts of the drugs can be tailored to match the metabolic profile of a patient's tumor.

The research also revealed a specific biochemical test that pathologists could use to guide such treatments. The test involves measuring the ratio between the amount of glutamine that a cell takes up from outside and the amount of glutamine it makes internally.