Rockefeller University researchers find nutrient that cancer cells crave

A team of researchers has found that arginine, an amino acid produced naturally by our bodies, is a key nutrient for cancer cells, and depriving those cells of the food they crave could make tumors more susceptible to the body’s natural immune response. 

The research was published in Science Advances, according to a news release from the Rockefeller University. There researchers from Sohail Tavazoie’s Laboratory of Systems Cancer Biology found that in a number of human cancers, arginine is more limited, leading those cancer cells to seek other genetic options, including the manipulation of proteins to use amino acids more efficiently and drive mutations that could curb their reliance on arginine for growth. 

“By starving a cancer cell, perhaps you can promote the gain of new mutations that can then be recognized by the immune system,” said first author Dennis Hsu, a former member of Tavazoie’s Lab and now a physician-scientist at UPMC Hillman Cancer Center in Pittsburgh, in the university’s report. 

The researchers noted in the university’s report that arginine is a central player in a number of cellular processes, from nitrogen waste disposal to protein synthesis. They also noted it is one of a handful of amino acids that can regulate the reaction of immune cells to cancer and other triggers. 

Moreover, the report noted, arginine deficiency is connected to inflamed tissues in patients diagnosed with Crohn’s disease, ulcerative colitis and inflammatory bowel disease. It also noted that people with low levels of arginine are at risk for developing colon or stomach cancer.

While focusing on triplets of DNA bases armed with the blueprint for a single amino acid, researchers found arginine condons were missing during mutations more frequently than they should have been, and colorectal and stomach cancers demonstrated the most dramatic shortage of the amino acid. 

According to the report, Hsu and his co-authors were able to grow cancer cells in the lab and then deny them arginine, essentially starving them. As the cells multiplied, they started to mutate in an effort to find alternate methods of securing access to a supply of their favorite nutrient. 

Hsu noted in the report that key methods included boosting the amount of amino acid transporter proteins to help the cells consume arginine and other amino acids more effectively. These avenues proved to be limited and errors increased, leading to changes that included mutated genes and misshaped proteins, the university’s report noted. 

The researchers, however, found that the ability to push condons to do what is needed could ultimately be the downfall for the cancer cells. As they try to stay alive while deprived of nutrients, they undergo so many mutations that they started to look unusual to the immune system.

The university concluded that the researcher’s findings could have an impact on immunotherapy, with the starvation of cancer cells paving the way for new mutations that could be recognized by the immune system.