Research on a rare cancer exposes possible route to new treatments
Posted: November 27, 2014 at 5:42 pm
PUBLIC RELEASE DATE:
26-Nov-2014
Contact: Linda Aagard 801-587-7639 University of Utah Health Sciences @UofUHealthCare
SALT LAKE CITY--Researchers from Huntsman Cancer Institute (HCI) at the University of Utah (U of U) discovered the unusual role of lactate in the metabolism of alveolar soft part sarcoma (ASPS), a rare, aggressive cancer that primarily affects adolescents and young adults. The study also confirmed that a fusion gene is the cancer-causing agent in this disease. The research results were published online in the journal Cancer Cell Nov. 26, 2014.
ASPS tumor cells contain a chromosomal translocation--strands of DNA from two chromosomes trade places. The two strands fuse together to create a new gene, ASPSCR1-TFE3 that functions differently than either "parent" gene.
For the study, Kevin B. Jones, MD, an HCI investigator and assistant professor in the Department of Orthopaedics at the U of U, and his research team activated the ASPSCR1-TFE3 gene in mice. The cancer was completely penetrant; every mouse with the activated fusion gene developed a tumor.
"The mouse tumors were remarkably similar to human ASPS tumors," said Jones. "The fusion gene not only initiates a cancer in the mouse, it initiates all the features we associate with this cancer in humans, including nearly identical RNA profiles." This is especially important in the study of sarcoma, as few human cell lines exist.
Jones said one surprising finding of the study was the location of the tumors in mice. In humans, most ASPS tumors occur in skeletal muscle, but all the mouse tumors occurred within the skull--"not necessarily in brain tissue, but within the environment of the cranium.
"The two places where we found most of the mouse tumors--inside the brain and inside the orbit of the eye--had the highest concentrations of lactate," said Jones. "The tissues where ASPS occurs in humans, the skeletal muscles, also have high concentrations of lactate."
Most cancer cells generate their energy in a process called glycolysis, in which they rapidly but inefficiently consume glucose. This process creates lactate as a waste product that the cancer cells push out into their surroundings.
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Research on a rare cancer exposes possible route to new treatments