St. Jude finds signaling system that halts the growth of a childhood brain cancerMarch 17, 2008Researchers discover that proteins BMP2, BMP4 and BMP7 inhibit the growth of medulloblastoma tumors, while inducing malignant cells to develop into normal neurons, a finding that may lead to better treatments for the cancer 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. Medulloblastoma occurs in the cerebellum, which is located in the lower, rear part of the brain. This cancer strikes about 350 young children in the United States annually. Although treated patients have an overall five-year survival rate of 70 percent, conventional therapies combining surgery, irradiation and chemotherapy frequently lead to permanent neurocognitive impairment. 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. "We were interested in whether there were signals that inhibited tumor formation," Roussel said. "And if there were, which ones were they? Could they be used to identify new therapeutic targets?" 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 did not carry the gene for Math1 failed to develop cerebellums. 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. BMPs, however, are extremely expensive to purify. Currently, the St. Jude researchers are searching for tiny, less expensive biological molecules that might mimic the action of BMPs in medulloblastoma. Roussel also suggests that the ability of BMPs to transform medulloblastoma cells into normal neurons, coupled with a discovery made earlier at St. Jude, could offer a combination treatment for the cancer. In 2004, a St. Jude team reported that an experimental drug called HhAntag, which inhibits Sonic hedgehog signaling, led to the deaths of medulloblastoma cells and the elimination of these tumors in treated mice. However, the team also found that treatment with HhAntag interfered with bone development in the animals, suggesting an unwelcome side effect in young children. Roussel's group reported that although both the Sonic hedgehog and BMP pathways play roles in regulating cell division, they do so in distinctly different ways. This led to testing the two in combination. "What we a found is that using a lower dose of the Sonic hedgehog inhibitor in combination with BMP gives the same therapeutic effect as high doses of the hedgehog inhibitor," Roussel said. "We hope that by reducing the levels of both compounds, we might prevent the secondary effects on bone of this potential therapy." St. Jude Children's Research Hospital Science News and Science Current Events Tag Cloud This tag cloud is a visual representation of term frequencies of random science news topics with common terms grouped together and emphasized by their display size. Metastasis Myeloma Nuclear Caffeine Human Papillomavirus Paleontology Lead Poisoning High Blood Pressure Brain Activity Cyclones Nanotubes Cancer Diagnosis Preterm Infants Epstein-barr Virus Clostridium difficile Jellyfish Osteoporosis Rheumatoid Arthritis Obstructive Sleep Apnea MicroRNA Prions Quantum Snoring Sinkhole Spinal Cord
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Related Medulloblastoma Current Events and Medulloblastoma News Articles New tumor markers determine therapy intensity Characteristic changes in the DNA of medulloblastoma, the most frequent malignant brain tumor in childhood, indicate precisely how aggressively the tumor will continue to spread and what the chances of disease relapse are. Researchers discover gene mutations that cause childhood brain cancer Researchers funded by the Canadian Cancer Society have discovered eight similar genes that, when mutated, appear to be responsible for medulloblastoma - the most common of childhood brain cancers. The findings are published today in the online edition of the journal Nature Genetics. Cancer cells with a long breath: seeking the origin of brain tumors in children Medulloblastoma is one of the most common and most malignant brain tumours among children and teenagers. These tumours grow very rapidly, and fifty percent of patients in the long term die from the condition. Childhood brain tumor traced to normal stem cells gone bad An aggressive childhood brain tumor known as medulloblastoma originates in normal brain "stem" cells that turn malignant when acted on by a known mutant, cancer-causing oncogene, say researchers from Dana-Farber Cancer Institute and the University of California, San Francisco (UCSF). Certain anticancer agents could be harmful to patients with heart disease A set of promising new anticancer agents could have unforeseen risks in individuals with heart disease, suggests research at Washington University School of Medicine in St. Louis. Protein protects embryonic stem cells' versatility and self-renewal A protein known as REST blocks the expression of a microRNA that prevents embryonic stem cells from reproducing themselves and causes them to differentiate into specific cell types, scientists at The University of Texas M. D. Anderson Cancer Center report in the journal Nature. St. Jude defines eye cancer gene's role in retinal development A genetic discovery led by scientists at St. Jude Children's Research Hospital helps answer a long-standing mystery about the eyes of vertebrates, and may translate into a deeper understanding of how genes coordinate the complex process of eye formation and how a rare pediatric eye cancer progresses. Statin plus cancer drug deliver combo punch to brain cancer cells Building on newly discovered genetic threads in the rich tapestry of biochemical signals that cause cancer, a Johns Hopkins Kimmel Cancer Center team has dramatically killed brain cancer cells by blocking those signals with a statin and an experimental antitumor drug. Brain tumor researchers find their 'niche' Brain tumors appear to arise from cancer stem cells (CSCs) that live within microscopic protective "niches" formed by blood vessels in the brain; and disrupting these niches is a promising strategy for eliminating the tumors and preventing them from re-growing. Prenatal vitamins may reduce risk of brain tumors in children Women who take multivitamins early in pregnancy may reduce the risk that their child will develop some types of brain tumors. More Medulloblastoma Current Events and Medulloblastoma News Articles |
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