Corporate Banner
Satellite Banner
RNAi
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

New Insights into Neuroblastoma Tumor Suppressor may Provide Clues for Improved Treatment

Published: Thursday, August 15, 2013
Last Updated: Thursday, August 15, 2013
Bookmark and Share
Loss of a gene required for stem cells in the brain to turn into neurons may underlie the most severe forms of neuroblastoma, a deadly childhood cancer of the nervous system.

Published in Developmental Cell today, the findings also provide clues about how to improve treatment of this often-incurable tumor.

Neuroblastoma can appear in nervous tissue in the abdomen, chest and spine, among other regions of the body, and can spawn body-wracking metastasis. The most severe tumors respond poorly to treatment and the disease accounts for 15 percent of cancer deaths in children.

Johan Holmberg, PhD, at the Ludwig Institute for Cancer Research Stockholm took a close look at the role of the CHD5 tumor suppressor during normal nervous system development. Previous studies had shown that the gene CHD5 is often inactivated in the most severe forms of neuroblastoma, but little was known about its function in healthy tissue or how it operates. The study, which was conducted in close collaboration with colleagues at Trinity College, Dublin, Ireland, addressed these two key issues.

The researchers found that CHD5 is required for the cellular transition from a stem cell to a mature neuron. In one experiment, the researchers knocked down the CHD5 gene by injecting a small RNA into the brains of fetal mice while in the womb.

"The result was a complete absence of neurons," says Ludwig researcher Holmberg who is based at the Karolinska Institutet. “Instead of becoming neurons, the cells with CHD5 knocked down stayed in a limbo-like state between an actively-dividing stem cell and a mature nerve cell. It was a very robust effect," added Holmberg.

The researchers also dissected how CHD5 operates, showing that it sticks to certain modifications of histone proteins. These modifications help control how genes are turned on and off. In the absence of CHD5, key stem cell genes are not turned off, and genes required for neuronal maturation are not turned on. The findings highlight how the failure of a cell to properly mature into its terminal state can underlie cancer, a relatively understudied area of research.

"It is necessary for cells in the healthy nervous tissue to be able to go from stem cells to neurons," explains Holmberg. "If you lose this capacity, these cells become locked in an immature state, which might yield quite dangerous tumor cells, especially in combination with additional cancer-promoting cellular events.”

The research could also lead to new ways to treat neuroblastoma, perhaps using currently approved drugs. One component of neuroblastoma treatment is retinoic acid, a drug that can drive neuronal maturation. Holmberg and his colleagues found that knocking down the expression of CHD5 in more benign neuroblastoma cells blocked their capacity to mature in response to retinoic acid treatment. "These cells were completely insensitive to treatment, no matter how much we gave them, mirroring the same unresponsiveness to retinoic acid in the more malignant CHD5-negative neuroblastoma cells,” says Holmberg.

The results of these cell-based experiments are consistent with clinical findings that retinoic acid is often unsuccessful in patients with severe forms of the disease. Holmberg reasons that if CHD5 could be re-activated in such hard-to-treat patients, it might increase responsiveness to retinoic acid. The findings may also have relevance for other types of tumors. For instance, CHD5 is often inactivated in glioblastoma multiforme, the most common and most aggressive form of brain cancer in adults.

Funding for this research came in part from Science Foundation Ireland; the Health Research Board; the Swedish Cancer Society, the Swedish Research Council, the Lilian Sagen and Curt Eriksson Research Foundation; DBRM; the Swedish Childhood Cancer Foundation; the Danish National Research Foundation; the Lundbeck Foundation; and the Novo Nordisk Foundation.

Holmberg is the head of the head of the CNS Tumors and Development lab at the Ludwig Institute for Cancer Research Stockholm where he is based at the Karolinska Institutet.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,500+ scientific posters on ePosters
  • More than 5,000+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Blood Pressure Drug May Boost Effectiveness of Lung Cancer Treatment
Researchers at Imperial College London have suggested that the blood pressure drug may make a type of lung cancer treatment more effective.
Developing Novel Ear Infection Treatments
Research team engineers antibiotic gel for treating middle ear infections.
Wearable Microscope Can Measure Fluorescent Dyes Through Skin
UCLA research could make monitoring disease biomarkers easier and more cost-effective.
Potential of New Insect Control Traits in Agriculture
Researchers have discovered a protein that shows promise as an alternate corn rootworm control mechanism.
Fighting Cancer with Sticky Nanoparticles
Treatment that uses bioadhesive nanoparticles drug carriers proved more effective than conventional treatments for certain cancers.
Fighting Plant Pathogens with RNA
Researchers develop strategy that could lead to environmentally friendly fungicide to fight pathogens.
Smart Material Hunts Cancers
Team has created smart material that locates and images cancer or tumour sites in tissue.
Examining mtDNA May Help Identify Unknown Ancestry That Influences Breast Cancer Risk
Researchers studying mtDNA in a group of triple negative breast cancer patients found that 13 percent of participants were unaware of ancestry that could influence their risk of cancer.
Gene Therapy Technique May Help Prevent Cancer Metastasis
Gene-regulating RNA molecules could help treat early-stage breast cancer tumors before they spread.
Enhancing Antibiotics to Defeat Resistant Bacteria
Scientists enhance ability of antibiotics to defeat resistant types of bacteria using molecules called PPMOs
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!