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Cancer is Addicted to Glycine

05/24/2012
Ashley Yeager

According to a new study, the amino acid glycine fuels fast-growing cancer cells. The discovery could re-shape current cancer treatments and make future therapies more targeted toward stopping dangerous cell growth.

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Body builders aren’t the only ones that gorge on protein. Fast-growing cancer cells take in extra amino acids to bulk up quickly too.

Food diaries from 60 human cancer cell lines show that they all consume large amounts of the amino acid glycine when growing fast. Scientists discovered the glycine gorge when they recorded the exact nutrients that fast and slow-growing cancer cells consumed each hour, according to their results published in the May 25 issue of Science (1). The result could lead to targeted anti-cancer drugs and possibly a test whether an individual's cancer is or is not bulking up at a fast pace.

This image shows a fluorescence micrograph of breast cancer cells, with proteins of the cell's cytoskeleton shown in red and the nucleus in blue. Source: Lutz Langbein, German Cancer Research Center.





"The glycine result was striking," said study author Vamsi Mootha, a systems biologist who holds joint posts at Massachusetts Institute of Technology, Harvard University, and Massachusetts General Hospital. His team did not expect to find that the doubling times of fast-growing cancer cells would parallel the cells' consumption of glycine. "It's not a perfect relationship, but it's quite strong, across multiple cancer types," he said.

To systematically describe the feeding habits of the cells, the team used liquid chromatography coupled with mass spectrometry. The results provided a consumption and release, or CORE, profile for 219 metabolites from the major pathways of cell metabolism.

The cells came from the NCI-60, a set of well-characterized human cell lines from nine common tumor types. Once the team developed the CORE profiles of the cells, they developed an atlas with information on the feeding patterns of each cell type. The scientists then began to look for metabolic signatures unique to each cancer. They also looked at whether any CORE profiles correlated to rapid cancer cell growth.

Two profiles—those of phosphocholine and glycine—stood out. Glycine, however, was an unexpected result because it is a non-essential amino acid that a cell can already produce itself. To further investigate glycine's role in cell growth, the team monitored how healthy, fast-growing epithelial cells used the amino acid.

"What their results imply is clear: Glycine is consumed by cancer cells but is released by normal cells," said Masaru Tomita, a molecular biologist and computer scientist at Keio University in Japan, who was not involved in the study. The reason fast-growing cancer cells consume so much glycine is not yet clear, he added.

Now, Tomita believes scientists should study the metabolites within the cells, in addition to the culture medium around them, to understand what is happening inside the cells. "A better understanding of how glycine metabolism is deranged in cancer may help us to continue to use these valuable drugs but perhaps improve their side effect profiles," said Mootha.

References

1. Jain M, et al., 2012. Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 336:1040-1044.

Keywords:  cancer biology