Navigation Links
St. Jude finds signaling system that halts the growth of a childhood brain cancer
Date:3/14/2008

A discovery by St. Jude Childrens 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 brains 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 papers 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.

Roussels 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.


'/>"/>

Contact: Summer Freeman
summer.freeman@stjude.org
901-495-3061
St. Jude Children's Research Hospital
Source:Eurekalert

Related medicine news :

1. Survey Finds Many Americans Clueless About Eye Disease
2. Rodent study finds artificial butter chemical harmful to lungs
3. Damaged veins heal faster with heparin treatment, laboratory study finds
4. Study Finds Naturopathic Care for Chronic Low-Back Pain to be Efficacious, Cost-Effective
5. Large Disparities in Kidney Testing Based on Disease, Gender and State, Quest Diagnostics Health Trends(TM) Report Finds
6. Early bird doesnt always get worm, UNC researcher finds
7. Gender bias may affect care of people with osteoarthritis, study finds
8. Drosophila drug screen for fragile X syndrome finds promising compounds and potential drug targets
9. New Harris Survey Finds That Most Baby Boomers Underestimate Disability Risk
10. FDA Finds Contaminant in Baxters Recalled Heparin Products
11. Aromatherapy Falls Short, Study Finds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... ... agency serving communities in the greater Dallas, Miami, and Raleigh regions, is organizing ... fighting to overcome a rare and deadly chromosome abnormality. , After struggling since ...
(Date:10/13/2017)... ... October 13, 2017 , ... The International ... promote standards of excellence for the field of eating disorders, announces the opening ... 25, 2018 in Orlando, Florida at the Omni Resort at ChampionsGate. ...
(Date:10/13/2017)... ... , ... Many families have long-term insurance that covers care for a family ... for care if the client has a cognitive impairment diagnosis. , “What this ... often waived, so the benefits from their insurance start immediately,” said Mechell Vieira, owner ...
(Date:10/13/2017)... ... October 13, 2017 , ... ... giving viewers the lowdown on sciatica in a new episode of "Success Files," ... on current events and innovation and investigates each subject in-depth with passion and ...
(Date:10/12/2017)... ... October 12, 2017 , ... CitiDent and San Francisco dentists, ... cutting-edge Oventus O2Vent technology. As many as 18 million Americans are estimated to ... breathing. Oral appliances can offer significant relief to about 75 percent of people ...
Breaking Medicine News(10 mins):
(Date:10/10/2017)... --  West Pharmaceutical Services, Inc. (NYSE: WST), a ... today shared the results of a study highlighting the ... administration of polio vaccines. The study results were presented ... by Dr. Ondrej Mach , Clinical Trials and ... and recently published in the journal Vaccine. i ...
(Date:10/4/2017)... SEOUL, South Korea , Oct. 4, 2017 /PRNewswire/ ... launched its next-generation CPR training aide "cprCUBE" on Kickstarter. ... of chest compression during cardiac arrests with better efficiency ... patient-mannequins. It also offers real-time feedback on efficacy of ... The crowdfunding campaign has a goal to raise ...
(Date:10/2/2017)... 2, 2017 Diplomat Pharmacy, Inc. (NYSE: ... and Consulting, LLC , and named its founder as ... in Tennessee , will operate under ... EnvoyHealth,s service offerings for health care partners to include ... "In an interoperable world, technology delivers ...
Breaking Medicine Technology: