Tag Archives: cancer growth

Amino Acids – Their Role in Aggressive Brain Cancer

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.

Reference:

http://www.dkfz.de/en/presse/pressemitteilungen/2013/dkfz-pm-13-35-Brain-Cancer-Hunger-for-Amino-Acids-Makes-It-More-Aggressive.php

Glycine Metabolism: Cancer Targeting Treatment?

Are we now able to peek into dangerous areas, like cancer, that would normally kill us? Scientists are having a look at glycine metabolism and its role in cancer growth. Researchers in Boston investigated the mutations cells undergo when healthy cells are mutated into cancer cells, and looked into possible ways of targeting these cancer cells.

Cancer occurs when previously healthy cells mutate, proliferating—replicating–rapidly. In fact, the definition of cancer is a malignant neoplasm, which refers to a group of diseases involving unregulated cell growth. The cancer cells divide and grow uncontrollably, forming malignant tumors which are often fatal. Rapidly proliferating cancer cells can spread to other parts of the body through the bloodstream or lymphatic system.

Very simply put, cancer can spread so rapidly because cancer cells reprogram normal, healthy cells. Mohit Jain, Roland Nilsson, et al, researchers with Harvard Medical School, Boston, USA, wanted to examine this metabolic reprogramming of cancer cells.

They studied 60 well-characterized human cancer cell lines, from nine common tumor types, to characterize cancer cell metabolism. The researchers profiled the cellular consumption and release of over 200 metabolites, the molecules which are necessary for metabolism.

Link between glycine metabolism and cancer cells

In the in vitro experiment, cancer cell lines were cultured, and their metabolites were measured. The researchers found a significant correlation between glycine consumption and cancer cell proliferation.

Glycine is a non-essential amino acid, which can be synthesized by our bodies. In the study, glycine was consumed by rapidly proliferating cells, and released by slowly proliferating cells. This means that glycine is demanded by the cancer cells. The glycine consumption was pronounced in ovarian, colon, and melanoma tumor cells.

The researchers discovered that the glycine biosynthetic pathway was closely linked to cancer cell proliferation, meaning that the cancer was relying on glycine to spread. This increased reliance could make the cancer cells metabolically vulnerable to specific targeting.

The study concluded that this metabolism of glycine could be used to target the rapidly proliferating cancer cells, possibly becoming a new anti-cancer treatment.

Sources:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526189/