Research
Seeking the Seeds of Cancer

Are all cells in a brain tumor created equal? Or could a few "bad seeds" be the ones causing all the trouble? If you could zero in on those culprit cells, could you stop the whole tumor from growing?

That is the hope behind the research of Stephen Huhn, M.D., chief of pediatric neurosurgery at Packard Children's Hospital. As the Arline and Pete Harman Faculty Scholar, Huhn is using a three-year grant to scrutinize tissue from brain tumors, seeking the seeds of cancer in a still-murky phenomenon called the "cancer stem cell." His early findings, presented in February at the annual conference of the American Society of Pediatric Neurosurgery, support an exciting new view of cancer biology.

Stephen Huhn, M.D., chief of pediatric neurosurgery at Packard, is tackling children's brain cancer in both the operating room and the laboratory. He is studying the possible role of a "cancer stem cell" in the development of brain tumors.

Huhn is trying to solve a basic riddle: the cellular origin of brain cancer. "We want to identify the abnormal neural [brain] cell from which other tumor cells arise," he says. "In other cancers, there is evidence to suggest the existence of a cancer stem cell—in particular, studies of leukemia and breast cancer—so we’re asking that question now in brain tumors. We think there may be a small population of cells in a brain tumor that have a much higher capacity for growth, and that those cells could represent cancer stem cells."

What difference would this make for children with brain cancer? "If we can confirm the concept of cancer stem cells in brain tumors, then the target cell for future therapies may in fact be the cancer stem cell," Huhn says.

A cancer stem cell differs from a regular stem cell in one simple way: its proliferation is out of control. Normally, stem cells' regenerative process remains tightly limited, but cancer stem cells may elude that control.

In his tissue study, Huhn looked at cells from a variety of pediatric and adult brain tumors. "In all types of tumors, we found tumor cells that carry cellsurface markers shared by normal neural stem cells. The marker seems to be more common in malignant tumors than benign ones, and it may be more common in the pediatric tumors."

His group is now developing an animal model to test whether these select cells within the tumor are in fact more likely to become cancerous than the other tumor cells. Do they lead to more tumor growth compared with cells that lack these surface markers?

"We need to be cautious in making predictions here, because all of this is in the very early stages," says Huhn. He speculates, however, that current treatments might sometimes fail because they don't adequately combat cancer stem cells, or because cancer stem cells are more treatment-resistant than other tumor cells. "We could potentially design new therapies specifically to stop the growth of the cancer stem cells," Huhn says. "And if we can stop the cancer stem cells, then in fact we may control the tumor."