“Glutamine Addiction” Fuels Melanoma

Melanoma cells proliferate and thrive when they have access to glutamine. Without the protein building amino acid, these cancerous cells die, according to new research.

The study, published February 17, 2015 in Oncotarget, suggests melanoma cells use glutamine, an essential nutrient, as a source of energy and carbon. 

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“We have shown for the first time how glutamine is metabolized by melanoma cells and how their appetite for it is driven by the tricarboxylic acid (TCA) cycle,” senior author David Scott, Ph.D., a scientist at Sanford-Burnham Medical Research Institute, La Jolla, Calif., says in a press release. 

The TCA, or Krebs, cycle, is a metabolic cycle that occurs in the mitochondria of cells to generate chemical energy in the form of ATP-the high-energy molecule that provides the fuel for cells to carry out their functions. Normally, glutamine creates a nitrogen supply for cells, according to the release.

“Their requirement for glutamine is in contrast to the nutritional requirements of normal melanocytes and is completely independent of the DNA mutations such as BRAF, NRAS, and p53 that transform healthy melanocytes to become tumorigenic,” Dr. Scott says.

NEXT: The knowledge could lead to treatments

The knowledge could lead to treatments-even nutritional strategies--focused on limiting glutamine supply to tumors. The finding suggests a glutamine starvation approach might work broadly against many melanoma tumors, says lead author and Sanford-Burnham scientist Boris Ratnikov, Ph.D.,.

“Melanoma’s addiction to glutamine is like an Achilles’ heel. It represents a vulnerability that we can target while sparing normal melanocytes that can survive without glutamine,” Dr. Scott says.

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While the approach might be novel in melanoma, it has a proven track record in other cancers. The amino acid starvation strategy is successful for treating certain types of leukemia, according to Dr. Scott.

“Our new study clearly shows how, at least in vitro, melanoma cells are dependent on glutamine for growth and survival. Our next step is verify our findings in vivo and ultimately test therapeutic strategies that restrict tumor access to glutamine,” study author Andrei Osterman, Ph.D., professor in bioinformatics and structural biology at Sanford-Burnham, writes in an email to Dermatology Times.

References

Ratnikov Boris, Aza-Blanc Pedro, Ronal A. Ze’ev, Smith W. Jeffrey, Osterman L. Andrei, Scott A. David, Glutamate and asparagine catapierosis underlie glutamine in melanoma. Oncotarget. 2015;14(2): Link