Altered Metabolism of Four Compounds Drives Glioblastoma Growth
News Apr 22, 2016
The altered metabolism of two essential amino acids helps drive the development of the most common and lethal form of brain cancer, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).
The study shows that in glioblastoma (GBM), the essential amino acids methionine and tryptophan are abnormally metabolized due to the loss of key enzymes in GBM cells.
The altered methionine metabolism leads to activation of oncogenes, while the changes in tryptophan metabolism shield GBM cells from detection by immune cells. Together, the changes promote tumor progress and cancer-cell survival.
“Our findings suggest that restricting dietary intake of methionine and tryptophan might help slow tumor progression and improve treatment outcomes,” says first author and OSUCCC – James researcher Kamalakannan Palanichamy, PhD, research assistant professor in Radiation Oncology.
“While we need to better understand how these abnormally regulated metabolites activate oncogenic proteins, our intriguing discovery suggests novel therapeutic targets for this disease,” says principal investigator and study leader Arnab Chakravarti, MD, chair and professor of Radiation Oncology and co-director of the Brain Tumor Program.
“For example, restoring the lost enzymes in the two metabolic pathways might slow tumor progression and reduce aggressiveness by inactivating oncogenic kinases and activating immune responses,” says Chakravarti, who holds the Max Morehouse Chair in Cancer Research.
Chakravarti further notes that because GBM cells take up methionine much faster than normal glioma cells, positron emission tomography that uses methionine as a tracer (MET-PET) might help map GBM tumors more accurately, allowing more precise surgical removal and radiation therapy planning. (MET-PET is currently an experimental imaging method.)
More than 11,880 new cases of GBM were estimated to occur in 2015, with overall survival averaging 12 to 15 months, so there is an urgent need for more effective therapies.
Amino acids are the building blocks of proteins. Tryptophan and methionine are essential amino acids – the diet must provide them because cells cannot make them. Normally, the lack of an essential amino acid in the diet can lead to serious diseases and even death. Foods rich in tryptophan and methionine include cheese, lamb, beef, pork, chicken, turkey, fish, eggs, nuts and soybeans.
Palanichamy, Chakravarti and their colleagues conducted this study using 13 primary GBM cell lines derived from patient tumors, four commercially available GBM cell lines and normal human astrocyte cells. Metabolite analyses were done using liquid chromatography coupled with mass spectrometry.
Simple Sugar Prevents Neurodegeneration in Lysosomal Storage DiseaseNews
New therapeutic approach may one day delay neurodegeneration typical of a disease called mucopolysaccharidoses IIIB (MPS IIIB)READ MORE
Eating Activates Calorie-Burning FatNews
The importance of the human brown adipose tissue (BAT) has become clearer during the past ten years. Coldness is one of the most effective activators of the BAT metabolic function but, in rodents, eating has also been shown to activate BAT. The debate on whether eating has the same effect on humans has lasted for decades. Now, the researchers at Turku PET Centre have proven that having a meal increases oxygen consumption in human BAT to the same extent as coldness.READ MORE
Penn Medicine Biochemist Receives Major Award for Research on Epigenetic Protein Modifications via Mass SpecNews
Benjamin A.Garcia, PhD, an expert in quantitative proteomics and Presidential Professor of Biochemistry and Biophysics in the Perelman School of Medicine at the University of Pennsylvania, has been awarded the Biemann Medal by the American Society for Mass Spectrometry (ASMS). The early-career award recognizes significant achievement in basic or applied mass spectrometry.