Glioma stem cells, which give rise to deadly brain cancers, have a metabolic state that differs significantly from that of the cancer cells they give birth to, a factor that helps these stem cells avoid treatment and cause recurrences later.
Researchers with the department of radiation oncology at UCLA's Jonsson Comprehensive Cancer Center also found for the first time that these glioma stem cells can change their metabolic state at will, from glycolysis (which uses glucose) to oxidative phosphorylation (which uses oxygen).
The stem cells' ability to change their metabolic state allows them to evade treatment and remain alive, said Dr. Frank Pajonk, a UCLA associate professor of radiation oncology and senior author of the study.
"We found these cancer stem cells are substantially different in their metabolic states than the differentiated cancer cells they create, and since they act differently, they can't be killed in the same way," he said. "And as yet, we don't have anything to target these glioma stem cells specifically."
The study was published this week in the early online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.
Cancer cells take up large amounts of glucose, which fuels their growth and helps them spread. It also allows them to be differentiated from normal, healthy cells during positron emission tomography (PET) scanning, which captures metabolic activity. But Pajonk and his team found that the glioma stem cells took up much less glucose than the cancer cells, making them difficult to detect with PET.
While the targeting of cancer metabolic pathways as a treatment has gained new interest in recent years, cancer stem cells that take up less glucose could evade treatments by utilizing glucose more efficiently through oxidative phosphorylation, which would not be targeted by such drugs.
"If glioma stem cells are indeed important for tumor control, knowledge of the metabolic state of glioma stem cells is needed," the study states.
Pajonk and his team developed a unique imaging system for glioma stem cells that relies on the low enzymatic activity of the proteasome in cancer stem cells. Using this system, they were able to assess the glioma stem cells for metabolic function, including oxygen consumption rates, glucose uptake and other markers.
They also found that the glioma stem cells were resistant to radiation, another roadblock to targeting these cells with conventional treatments.
The researchers concluded that glioma stem cells rely mainly on oxidative phosphorylation for energy. But they found that if the stem cells were challenged, they could switch on additional metabolic pathways.
The study also shows for the first time that low expression of proteasome sub-units, an indicator of large numbers of glioma stem cells in a tumor, predicts unfavorable treatment outcomes for patients.
"What I think is really exciting is we have here, for the first time, a novel cancer stem cell marker in glioma, which gives us an additional tool to look for these cells and come up with therapies that target them," said Pajonk, who also is a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
The study was funded by the National Cancer Institute.
UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson Center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2011, the center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 of the last 12 years.