Breast cancer cells recycle ammonia waste as fuel

According to the latest research, breast cancer cells recycle ammonia, a waste byproduct of cell metabolism, and use it as a source of nitrogen to fuel tumor growth. The presence of ammonia accelerates proliferation of cultured breast cancer cells, while suppressing ammonia metabolism can stunt tumor growth in mice.

This showed the biological role of ammonia in cancer and may inform the design of new therapeutic strategies to slow tumor growth. Ammonia is 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.

Cancer cells consume nutrients voraciously and generate excess metabolic waste. One such byproduct, ammonia, is normally transported in blood vessels to the liver, where it is converted into less toxic substances and excreted from the body as urea.Tumors have few blood vessels, and as a result, ammonia accumulates in the tumor's local environment at concentrations that would be toxic for many cells.

When glutamine is broken down during cell metabolism, ammonia containing nitrogen is released as a byproduct.
Tracing the fate of this marked ammonia, the researchers examined different cellular metabolites in breast cancer cells and in human tumors transplanted into mice. They found cancer cells recycled ammonia with high efficiency, incorporating it into numerous components-primarily the amino acid glutamate, a fundamental building block for proteins, as well as its derivatives.

Higher concentrations of ammonia appeared to accelerate the growth of lab-grown breast cancer cells. Ammonia exposed cells doubled up seven hours faster than cells grown without ammonia. In 3-D cultures-a technique that allows cells to divide in all directions as they do inside the body, ammonia exposure increased the number of cells and surface area of cell clusters by up to 50 percent compared with cells grown without ammonia.

Ammonia also accelerated tumor growth and proliferation in mice with transplanted human breast cancer. When the team blocked the activity of glutamate dehydrogenase GDH-an enzyme that specifically assimilates ammonia to carry out its function, tumor growth slowed significantly compared to tumors with intact GDH activity. Repressing ammonia metabolism stunts tumor growth in mice.
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