WBCR-LP 97.7FM, Great Barrington Community Radio
March 16 2008
MEMPHIS, Tenn., March 14 /PRNewswire-USNewswire/—A discovery by St.
Jude Children’s Research Hospital scientists suggests a safer way to treat
medulloblastoma, a rare but often fatal childhood brain tumor. The group
found that one of the brain’s signaling pathways inhibits the growth of the
highly aggressive cancer cells.
The researchers discovered that three proteins, designated BMP2, BMP4
and BMP7, halted the growth of medulloblastoma tumors and induced the
malignant cells to develop into normal neurons.
“We think we have identified a pathway that can be used to prevent
tumor formation and a potential target for therapy,” said Martine F.
Roussel, Ph.D., a member of the St. Jude Department of Genetics and Tumor
Cell Biology. A report on this work appears in the March 15 issue of “Genes
& Development.” Roussel is the paper’s senior author. Several research
teams are seeking to decipher the intricate signaling mechanisms that
govern the proliferation of cells called granule neuron progenitors (GNPs).
These cells go on to develop into neurons in the cerebellum during the
first year of life. But the disruption of this differentiation process can
trigger medulloblastoma.
Previous research had shown that spurring GNPs to differentiate into
neurons requires that BMPs bind to a set of receptors on the cell surface.
This binding results in blocking the activity of a signaling pathway
triggered by another molecule called Sonic hedgehog.
“What was not known, and what we now find, is that the effect of BMPs
on normal GNP cells is almost exactly mimicked in GNP-like tumor cells,”
Roussel said.
In cell culture experiments, her group found that BMPs rapidly cause
the degradation of a protein called Math1, which occurs in dividing GNPs,
but not in non-proliferating neurons. Twelve hours after BMP treatment,
researchers could detect no Math1 and cell growth soon stopped.
The exact way Math1 works remains unknown. However, in mice the protein
is vital to the formation of a normal brain. Mice genetically altered so
they do not carry the gene for Math1 failed to develop cerebella.
The St. Jude team also performed gene transfer experiments in mice to
test BMPs as a possible medulloblastoma treatment. Using a genetically
altered virus, scientists inserted the BMP gene into the cancer cells and
showed that the transfer not only halted tumor growth, but induced the
cancer cells to change into neurons.
Other authors of this study include Haotian Zhao, Olivier Ayrault and
Frederique Zindy (St. Jude) and Jee-Hae Kim (Rockefeller University, New
York).
This work was supported by the National Institutes of Health, a Cancer
Core Grant, La Fondation pour la Recherche Medicale, the Gephardt Endowed
Fellowship Signal Transduction and ALSAC.
St. Jude Children’s Research Hospital