There is an enzyme that causes the breakdown of certain amino acids, which makes brain cancer aggressive. Scientists have discussed their findings in the Nature Medicine journal. These researchers from the German Cancer Research Center (DKFZ) were looking for new kinds of therapies against aggressive brain cancer when they discovered the amino acids hunger is increased in certain forms of brain cancer.
Tumors that grow quickly and aggressively need more energy feeding them than regular (non-aggressive) brain cancer tumors. Tumors also need the right molecular building blocks to build the components of the cells in order to grow. Cancer is now known to feed on sugar (glucose), and some tumors can also catabolize glutamine, which is an amino acid.
Amino acids and role of enzymes in aggressive tumors
Primary glioblastomas are extremely malignant brain tumors. Glioblastomas also have a connection with the two enzymes BCAT1 and IDH (isocitrate dehydrogenase) because these enzymes cooperate together in decomposing branched-chain amino acids.
Amino acids are the building blocks of proteins, and these proteins can act as a food sources that increase the hunger, or aggressiveness, of cancer cells. For the first time, these scientists have been able to show that branched-chain amino acids have a significant role in the aggressive growth of certain malignant tumors.
Some years ago some researchers found gene coding mutations in IDH for a number of types of brain cancers, such as glioblastomas. If they lacked the IDH gene, then they would grow more slowly due to being defective. Radlwimmer, from the German Cancer Research Center, said that, “we can see that overexpression of BCAT1 contributes to the aggressiveness of glioblastoma cells.”
Their team compared the activity of genes from several hundred brain tumors to find out if intact or altered IDH enzymes had characteristics that might explain the aggressive tumor growth. They did, in fact, find a significance difference between two groups studied. The BCAT1 enzyme in a normal brain breaks down branched-chain amino acids, producing ketoglutarate (BCAT1 needs this molecule). So only intact IDH in tumor cells have the BCAT1 enzyme, so Bernhard Radlwimmer says, “The two enzymes seem to form a kind of functional unit in amino acid catabolism.”
Glioblastomas are what makes the brain cancer tumors particularly aggressive, and when the effects of BCAT1 is blocked, the tumor cells lose their capacity to grow or invade the healthy brain tissue. Also, at that point the cells also release less of the amino acid neurotransmitter—glutamate. When someone has brain cancer they often will get epileptic seizures, which are associated with high glutamate amino acid levels.
Because of this association, and how the researchers understand it now, agents are being searched for to target against the enzymes that are responsible for the aggressive tumor growth. BCAT1 expression is also being studied since it may be a marker to help diagnose brain cancer malignancy.