A study led by Marcia Hiagis, investigator at the Ludwig Center at Harvard, finds that breast cancer cells recycle ammonia—a toxic byproduct of cell metabolism that tends to accumulate in breast tumors—to fuel tumor growth.

The findings, published online in the journal Science ahead of print, show that ammonia accelerates proliferation of cultured breast cancer cells and that suppressing ammonia metabolism can stunt tumor growth in mice. When the team blocked the activity of glutamate dehydrogenase (GDH)—an enzyme critical to the assimilation of ammonia—tumor growth slowed significantly compared to tumors with unaltered GDH activity.

Rapidly growing cells, particularly cancer cells, consume nutrients voraciously and generate excess metabolic waste. Ammonia is normally transported to the liver, detoxified and excreted from the body as urea. Tumors, however, have few blood vessels, so ammonia accumulates in the tumor's local environment at concentrations that would be toxic for many cells. Haigis and her colleagues found, however, that cancer cells recycled ammonia with high efficiency, incorporating it into numerous components—primarily the amino acid glutamate, a fundamental building block for proteins. Around 20 percent of the cellular glutamate pool in their studies contained recycled nitrogen.

“We found that not only was ammonia not toxic for breast cancer cells, it could be used to feed tumors by serving as a source for the building blocks that tumors need to grow," said Haigis, who is also an associate professor of cell biology at Harvard Medical School.

The findings shed new light on the biological role of ammonia in cancer and may inform the design of new therapeutic strategies to slow tumor growth.