Navigation Links
Brain cancer: Hunger for amino acids makes it more aggressive
Date:6/24/2013

To fuel phases of fast and aggressive growth, tumors need higher-than-normal amounts of energy and the molecular building blocks needed to build new cellular components. Cancer cells therefore consume a lot of sugar (glucose A number of tumors are also able to catabolize the amino acid glutamine, an important building block of proteins. A key enzyme in amino acid decomposition is isocitrate dehydrogenase (IDH). Several years ago, scientists discovered mutations in the gene coding for IDH in numerous types of brain cancer. Very malignant brain tumors called primary glioblastomas carry an intact IDH gene, whereas those that grow more slowly usually have a defective form.

"The study of the IDH gene currently is one of the most important diagnostic criteria for differentiating glioblastomas from other brain cancers that grow more slowly," says Dr. Bernhard Radlwimmer from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). "We wanted to find out what spurs the aggressive growth of glioblastomas." In collaboration with scientists from other institutes including Heidelberg University Hospital, Dr. Martje Tnjes and Dr. Sebastian Barbus from Radlwimmer's team compared gene activity profiles from several hundred brain tumors. They aimed to find out whether either altered or intact IDH show further, specific genetic characteristics that might help explain the aggressiveness of the disease.

The researchers found a significant difference between the two groups in the highly increased activity of the gene for the BCAT1 enzyme, which in normal brain tissue is responsible for breaking down so-called branched-chain amino acids. However, Radlwimmer's team discovered, only those tumor cells whose IDH gene is not mutated produce BCAT1. "This is not surprising, because as IDH breaks down amino acids, it produces ketoglutarate a molecule which BCAT1 needs. This explains why BCAT1 is produced only in tumor cells carrying intact IDH. The two enzymes seem to form a kind of functional unit in amino acid catabolism," says Bernhard Radlwimmer.

Glioblastomas are particularly dreaded because they aggressively invade the healthy brain tissue that surrounds them. When the researchers used a pharmacological substance to block BCAT1's effects, the tumor cells lost their invasive capacity. In addition, the cells released less of the glutamate neurotransmitter. High glutamate release is responsible for severe neurological symptoms such as epileptic seizures, which are frequently associated with the disease. When transferred to mice, glioblastoma cells in which the BCAT1 gene had been blocked no longer grew into tumors.

"Altogether, we can see that overexpression of BCAT1 contributes to the aggressiveness of glioblastoma cells," Radlwimmer says. The study suggests that the two enzymes, BCAT1 and IDH, cooperate in the decomposition of branched-chain amino acids. These protein building blocks appear to act as a "food source" that increases the cancer cells' aggressiveness. Branched-chain amino acids also play a significant role in metabolic diseases such as diabetes. This is the first time that scientists have been able to show the role of these amino acids in the growth of malignant tumors.

"The good news," sums up Radlwimmer, "is that we have found another target for therapies in BCAT1. In collaboration with Bayer Healthcare, we have already started searching for agents that might be specifically directed against this enzyme." The researchers also plan to investigate whether BCAT1 expression may serve as an additional marker to diagnose the malignancy of brain cancer.


'/>"/>

Contact: Dr. Sibylle Kohlstädt
s.kohlstaedt@dkfz.de
Helmholtz Association of German Research Centres
Source:Eurekalert

Related medicine news :

1. Salk scientists discover previously unknown requirement for brain development
2. American Brain Tumor Association’s 2013 Patient & Family Conference Aims to Engage and Empower
3. hCGTreatments / Diet Doc hCG Diets & Weight Loss Plans Now Help Patients Lose Weight Fast and Reap Weight Loss Benefits Like Increased Brain Activity and Memory Function
4. Voices Against Brain Cancer Awards Grant to Tocagen to Support Investigation of Toca 511 & Toca FC in Patients with Recurrent Brain Cancer
5. Virus combination effective against deadly brain tumor, Moffitt Cancer Center study shows
6. RKNet Studio Launched Online Website for Fun Games, Brain Training and Cognitive Skills Development
7. Brain Not Working? Minor Symptoms Now Could Mean MS, Alzheimer's, or Parkinson's Later
8. Long-term study reports deep brain stimulation effective for most common hereditary dystonia
9. New Alzheimers research suggests possible cause: The interaction of proteins in the brain
10. American Brain Tumor Association Conference Advances Holistic Approach to Living with a Brain Tumor
11. Its the way you tell em: Study discovers how the brain controls accents and impersonations
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/21/2017)... ... January 21, 2017 , ... In the United States, 20 million women ... of recovery, they often feel shame for having struggled with an eating disorder as ... the workshop, “Rising Strong in Life After an Eating Disorder” -- to be featured ...
(Date:1/20/2017)... ... January 20, 2017 , ... A new partnership between Goodwill® and Roadie, Inc. ... or need, from clothes to couches to dressers and bicycles. Roadie — the national ... the nearest Goodwill donation center through February 28th. , “January is an exciting ...
(Date:1/20/2017)... ... ... Doctor C LLC, a company based out of Arizona that focuses on ... marketing and distribution of its product, The Right C. , The Right C is ... traditional vitamin C supplements. At the trade show, Doctor C had the opportunity to ...
(Date:1/20/2017)... (PRWEB) , ... January 20, 2017 , ... ... wellness products to enhance people’s everyday lives, recently attended the January ECRM Trade ... , ATP Science is known for its large range of supplements that keep ...
(Date:1/20/2017)... ... January 20, 2017 , ... "TransFlare 4K Mystique comes with 44 colorful mysterious ... X," said Christina Austin - CEO of Pixel Film Studios. , TransFlare 4K ... 4K Mystique lens flare and light leak transitions have a very high-dynamic range for ...
Breaking Medicine News(10 mins):
(Date:1/20/2017)... 2017 Research and Markets has announced ... Opportunities, and Future" report to their offering. ... This research service on the ... technologies, and provides a snapshot of the key participants in the ... are provided from 2016 to 2020. The market is expected to ...
(Date:1/20/2017)... -- Avillion LLP, a co-developer and financier of late-stage ... MD MBA as Chief Medical Officer. Dr Weinberg will be based ... ... spent more than 17 years as a pharmaceutical and biotech executive ... Over the course of his career, he has interfaced with the ...
(Date:1/19/2017)... , Jan. 19, 2017 The Global Therapy ... and access to partnering deals and agreements entered into ... in partnering deals - Top deals by value - ... development, technology type The report provides understanding and ... by the world,s leading healthcare companies. The report ...
Breaking Medicine Technology: