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Neurotransmitter NAAG helps cancer progress

April 25, 2019 16:15

Using human cancer cells, tumor and blood obtained from patients with cancer samples, researchers from Johns Hopkins Hospital have identified the role of a neurotransmitter in the spread of aggressive forms of cancer. Neurotransmitters - are chemical "messengers" that transmit impulses from the neuron to other cells, "target".

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New research has shown that the prevalence of neurotransmitter called N-acetyl-aspartyl-glutamate (NAAG) increases in cancer - high grade tumors - prone to rapid growth and metastasis. This makes it a potential marker of progression or regression of tumors during cancer therapy. Scientists have also demonstrated that NAAG is a source of glutamate, a chemical is used by cancer cells as building blocks to survive in tumors that express an enzyme called glutamate carboxypeptidase II (GCPII). They found that the termination GCPII activity with 2-PMPA preparation for the treatment of human ovarian tumors implanted at the ovaries of mice and tumor weight decreases the concentration of glutamate. Targeting GCPII, as well as targeting glutaminase, the enzyme that converts glutamate to glutamine, resulting in a significant reductionof human pancreatic tumors transplanted into the pancreas of mice.

Scientists suggest that NAAG is an important reservoir for the delivery of glutamate to cancer cells through GCPII.

The researchers conducted several laboratory experiments for the study of NAAG. At first, they used a mass spectroscopy for measuring glutamine degradation products and found that the production of NAAG was more common in advanced Burkitt's lymphoma cells, altered gene MYC cancer than in cells not modified MYC. They also found that NAAG was more common in cells of high malignancy of ovarian cancer, as compared with primary ovarian tumors. Scientists have observed a higher neurotransmitter concentration in samples of brain tumors, glioblastoma, and lower - in a slow-growing brain tumors, meningioma.

The findings suggest that NAAG may be used as a prognostic marker, a potential method of noninvasive assessment of tumor progression.

"Seven years ago, we found that glutamine plays an important role in the metabolism of cancer and the inhibition of the conversion of glutamine to glutamate may be used to inhibit cancer growth. However, this may not be enough, since cancer cells can output glutamamt through this hidden reservoir Targeting both pathways may improve cancer treatment "-. said the scientists.



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