In glioblastoma multiforme (GBM), the most common and lethal brain tumor, lack of differentiation makes a big, and bad, difference.
GBM tumors are full of cells that refuse to grow up, immature cells produced by cancer stem cells that fail at terminal differentiation -- the final step to becoming a mature, useful cell. These flawed precursor cells are a major source of cellular diversity, or heterogeneity, a hallmark of cancer that makes it hard to treat.
"If glioblastoma cells were to undergo differentiation, the tumor would stop growing," says Jian Hu, Ph.D., instructor in Genomic Medicine.
GBM cells are full of genetic events that promote stem cell-like activity. But Hu and colleagues wondered what might be missing from these tumors that would otherwise prevent such activity.
In research published this week in the online Early Edition of the Proceedings of the National Academy of Sciences, the researchers report gene circuitry that forces precursor cells to mature is deleted or impaired in glioblastoma.
"We've also shown that when this terminal differentiation circuitry is gone, precursor cells get stuck in the middle and produce many different cell types, causing tumor growth," Hu said.
The PNAS paper is the Inaugural Paper for senior author and MD Anderson President Ronald DePinho, M.D. Inaugural Papers are published in PNAS by newly elected members of the National Academy of Sciences. DePinho, who was elected in 2012, discusses this research in a PNAS interview also online.