Brain stem cells fuel the growth of brain tumors, say Washington
University School of Medicine researchers. Scientists showed in mice that disabling a gene linked to a common pediatric tumor disorder, neurofibromatosis type 1 (NF1), made stem cells from one part of the brain proliferate rapidly. But the same
genetic deficit had no effect on stem cells from another brain region.
The results can be explained by differences in the way stem cells
from these regions of the brain respond to cancer-causing genetic
NF1 is among the world's most common genetic disorders, occurring in
about one of every 3,000 births. It causes a wide range of symptoms,
including brain tumors, learning disabilities and attention deficits.
Brain tumors in children with NF1 typically arise in the optic nerve
and do not necessarily require treatment. If optic gliomas keep
growing, though, they can threaten the child's vision. By learning more
about the many factors that contribute to NF1 tumor formation,
scientists hope to develop more effective treatments.
"To improve therapy, we need to develop better ways to identify and
group tumors based not just on the way they look under the microscope,
but also on innate properties of their stem cell progenitors," says
David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of
The study appears July 9 in Cancer Cell
. Gutmann also is the
director of the Washington University Neurofibromatosis Center.
In the new study, researchers compared brain stem cells from two
primary sources: the third ventricle, located in the midbrain, and the
nearby lateral ventricles. Before birth and for a time afterward, both
of these areas in the brain are lined with growing stem cells.
First author Da Yong Lee, PhD, a postdoctoral research associate,
showed that the cells lining both ventricles are true stem cells capable
of becoming nerve and support cells (glia) in the brain. Next, she
conducted a detailed analysis of gene expression in both stem cell
"There are night-and-day differences between these two groups of
stem cells," Gutmann says. "These results show that stem cells are not
the same everywhere in the brain, which has real consequences for human
The third ventricle is close to the optic chiasm, the point where
the optic nerves cross and optic gliomas develop in NF1 patients. Lee
and Gutmann postulated that stem cells from this ventricle might be the
source of progenitor cells that can become gliomas in children with NF1.
To test the theory, they disabled the Nf1 gene in neural stem cells
from the third and lateral ventricles in the mice. This same gene is
mutated in patients with NF1, increasing their risk of developing
Lee found that loss of Nf1 activity had little effect on stem cells
from the lateral ventricle, but stem cells from the third ventricle
began to divide rapidly, a change that puts them closer to becoming
The third ventricle usually stops supplying stem cells to the brain
shortly after birth. When researchers inactivated the Nf1 gene before
the third ventricle closed, the mice developed optic gliomas. When they
waited until the third ventricle had closed to inactivate the Nf1 gene,
gliomas did not develop.
Gutmann plans further studies to determine whether all NF1-related
optic gliomas form in cells descended from the third ventricle. He
suspects that additional factors are necessary for optic gliomas to form
in cooperation with Nf1 gene loss in third-ventricle stem cells.
"We have to recognize that cancers which appear very similar
actually represent a collection of quite different diseases," he says.
"Tumors are like us — they're defined by where they live, what their
families are like, the traumas they experience growing up, and a variety
of other factors. If we can better understand the interplay of these
factors, we'll be able to develop treatments that are much more likely
to succeed, because they'll target what is unique about a specific