Frontier: Tracing a tumor source

by Sandra A. Swanson

September, 2008

Treatments exist for medulloblastoma, a common childhood brain tumor, but they wreak havoc on cognitive development. New research sheds light on the tumor’s origins and could lead to therapies targeted precisely at the root of the problem.

A study published Aug. 12 in Cancer Cell challenges assumptions about the source of medulloblastoma. Previously, cerebellar progenitor cells were accepted as medulloblastoma’s starting point. More mature than stem cells (which can produce many cell types), these progenitor cells produce only neurons.

“The problem is that medulloblastoma has a more complicated phenotype (observable traits shaped by genetic and environmental factors) than just neurons,” says Keith Ligon of the Dana-Farber Cancer Institute, one of the cosenior authors of the study. That fueled doubts about whether a single progenitor cell type was solely responsible.

Ligon and colleagues in San Francisco, Boston and Munich, Germany, used mice to systematically determine which cell types resulted in tumors. That meant reactivating the Sonic Hedgehog pathway. Named after a popular video game character, this cell-signaling pathway helps guide early brain development and then shuts down. If a mutation reactivates the pathway, it leads to non-stop cell division and tumor growth.

The results suggest that the tumors can develop from glial-like stem cells, as well as neuronal progenitors. The cell properties witnessed in mice resemble those in human tumors, Ligon says—providing a springboard to explore treatment and prevention. The researchers have isolated medulloblastoma cancerstem-cell lines from humans and areculturing them to use as a model system.

“Maybe the medulloblastomas look the same under the microscope, but each patient might have a different cell of origin,” Ligon says. “There may be new diagnostic categories we need to determine.”