Mammary Cancer Cells Can Make Use Of Waste From The Cell's Metabolism For Fuel
Mammary cancer is the highest incidence of cancer among women around the world. researchers have been exploring new therapies. One treatment strategy is to study the sources of cancer cells and to block them, thereby achieving the goal of starving cancer cells. Recently, researchers from Harvard medical school (HMS) found that mammary cancer cells can be recycled from waste by-product of cellular metabolism of ammonia, as a nitrogen source, to support the tumor growth. If the ammonia metabolism is artificially suppressed, tumor growth can be blocked in mice. The researchers say the findings reveal the role of ammonia in cancer and have the potential to inspire new treatment strategies that inhibit tumor growth. The paper was published in science.
"Ammonia is thought to be the waste of cellular metabolism because its high toxicity, it must be removed," he said. The senior author of the paper, Dr Marcia Haigis, associate professor of cell biology at HMS, said: "But we found that for mammary cancer cells, ammonia is non-toxic, moreover it can also be used as a feedstock for tumor growth. Rapidly growing cells, including cancer cells, consume a lot of nutrients and produce excess metabolic waste. Ammonia is a by-product. It is usually transferred to the liver via blood vessels, where it is converted into less toxic substances. It is then expelled from the body in the form of urea. However, there are very few blood vessels in the tumor, so ammonia can accumulate in the microenvironment of the tumor, which can be toxic to normal cells.
In order to see how tumors deal with high levels of ammonia, Haigis's team marks the nitrogen atoms in glutamine. When glutamine is broken down during cell metabolism, the labeled nitrogen is released as a by-product. Researchers analyzed that more than 200 different cell metabolites produced by breast cancer cells and human tumors transplanted into mice to track traces of the tagged ammonia. They found that the cancer cells can efficiently recycle ammonia and incorporate it into many components, mainly glutamate and its derivatives. They are one of the basic components that make up proteins. About 20 percent of cellular glutamate contains recycled nitrogen.
higher concentrations of ammonia seem to speed up the growth of mammary cancer cells in the lab. The cells exposed to ammonia were seven hours shorter in proliferation than those grown in an ammonia-free environment. In 3D culture, the cells exposed to ammonia were significantly increased compared with the cells without ammonia, and the number of cells and the surface area of the cell cluster increased significantly. Ammonia can also accelerate the growth of mammary cancer tumors in mice. The researchers also found that when the inhibited absorption of ammonia is required to complete various functions of the activity of glutamate dehydrogenase (GDH), tumor growth compared with GDH activity unaffected controls appear to slow significantly. " Inhibiting ammonia metabolism inhibits tumor growth in mice, "said Jessica Spinelli, lead author of the paper. "Therefore, inhibition of ammonia absorption or ammonia production may be a therapeutic strategy for rational design."
Wuxi "Recent progress summary of tumor field (phase 42)", 2017-10-30