Researchers from Washington University School of Medicine in St. Louis found that a neurotransmitter, named GABA ( gamma amino butyric acid ), shows up in unusually high amounts in some aggressive tumors.

The researchers investigated metastatic neuroendocrine tumors, which include aggressive types of lung, thyroid, and prostate cancers that spread to other parts of the body.

"GABA appears to be an indicator of a bad prognosis for these cancers," says Jeffrey I. Gordon, director of the Center for Genome Sciences at Washington University. " But there's hope in our ability to identify substances, like GABA, that are associated with metastatic tumors. Usually these tumors are diagnosed only after they have spread to other parts of the body, but now we have the potential to recognize them before they metastasize."

Elevated amounts of GABA were discovered in an analysis of aggressive neuroendocrine prostate tumors in genetically engineered mice.
Along with GABA, two other substances were seen, one a related neurotransmitter and the other a plant growth hormone with an unknown function in animals.
Furthermore, the researchers found that the tumors made GABA using a different set of biochemical reactions than normal.
Key enzymes involved in the production of these compounds were switched on in poor prognosis malignant metastatic tumors.

The researchers believe that metastatic neuroendocrine tumor cells use GABA signaling processes to communicate with each other and with their environment. " Through carefully planned clinical trials, we may be able to evaluate the therapeutic potential of already available drugs that affect GABA signaling to treat these aggressive types of cancers," says Ippolito.

They combined the mouse data with parallel data from 182 human tumors. Then, the gene-activity data was fed into sophisticated software that supplied the researchers with a prediction about which metabolic reactions were revved up in the tumors and which were slowed down. The last piece of the puzzle was supplied by a highly sensitive instrument, called a mass spectrometer, that measured the products of cellular metabolism. The mass spectrometer measurements were cross-checked with the gene activity data and the predictions of metabolic reactions. This set of techniques demonstrated the linkage of abnormal GABA production to aggressive tumors.

Source: Washington University School of Medicine, 2005


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