Abstract
Metabolic analysis of the NCI-60 human cancer cell lines has resulted in a large set of data about what nutrients cancer cells take up and release over time, and identified an important role for the amino acid glycine in the proliferation of cancers.
Metabolic analysis of 60 human cancer cell lines has produced a large set of data about what nutrients cancer cells take up and release over time. Researchers affiliated with Harvard Medical School and their colleagues who put together the dataset have used it to identify an important role for the amino acid glycine in the proliferation of cancers.
Most previous studies of cancer metabolism have provided a single snapshot of the nutrients and byproducts present in cells at one moment in time. These studies can provide information about the presence or absence of tens of thousands of metabolites within the cell but trying to understand them may be like trying to determine traffic flow in a city by looking at an aerial photograph.
To get a moving picture of cancer metabolism, the scientists created a database of metabolites consumed and released by cancer cells over time (Science 2012;336:1040–4.) The result is one of the first kinetic portraits of cancer-cell metabolism.
The group took measurements on the NCI-60, a collection of 60 human cancer cell lines from 9 tumor types, which let them leverage the large body of research already carried out on these cells, including an atlas of NCI-60’s gene-expression profiles. They took samples from the growth media supporting the cells and employed mass spectrometry to measure levels of 219 metabolites over time.
Vamsi Mootha, MD, professor of systems biology at Harvard Medical School and senior author on the study, hopes that other researchers will use the metabolomics data to find trends in the metabolic uptake and release data.
The association between glycine uptake and rapid proliferation of cancer cells was striking, says Mootha— particularly because noncancerous cells with comparable rates of proliferation were found to release glycine.
To identify the pathways that underlie the cancer cells’ reliance on glycine, scientists examined the gene-expression patterns of 1,425 metabolic enzymes in a previous NCI-60 study. Two pathways related to the amino acid stood out. When they silenced key enzymes in these pathways in 2 cancer cell lines, the proliferation rate slowed.
The researchers then turned to databases of gene expression in 1,300 patients with early-stage breast cancer. They found that above-median expression of 3 enzymes in the glycine-synthesis pathway were as strongly associated with mortality as are lymph node status and tumor grade.
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