Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Brain tumor growth requires abnormal neighbors

15.12.2003


For some brain tumors, the key to success is not just what you know but who you know, according to researchers at Washington University School of Medicine in St. Louis.



In trying to develop a mouse model of neurofibromatosis 1 (NF1), a genetic disorder that predisposes children to certain types of brain tumors, the team discovered that tumors only developed when all brain cells were genetically abnormal, not just the cell type that becomes cancerous. The study is featured on the cover of the Dec. 15 issue of the journal Cancer Research.

"We are quite excited about this report as it represents the first model of this type of tumor," says principal investigator David H. Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology. "We’ve always assumed that cancer results from the loss of specific genes in a particular cell, but apparently that isn’t always the case. Our findings suggest that as in real estate, location is everything – a permissive environment may be the key to whether a tumor cell becomes cancerous or just sits dormant for a person’s entire life."


According to the National NF Foundation, NF1 is the most common neurological disorder caused by a single gene. The disorder can lead to a variety of complications including skin, spine and brain cancer. Up to 20 percent of patients with NF1 develop tumors in a type of support cell called an astrocyte along the optic nerve and optic chiasm, which transmit visual information from the eye to the brain.

Astrocytes that develop into tumors lack both copies of the Nf1 gene. So Gutmann’s team first developed genetically engineered mice in which all cells were normal except astrocytes, which lacked both copies of the Nf1 gene. To their surprise, the mice did not develop brain tumors.

Humans with NF1 are born with one normal and one mutated copy of the Nf1 gene in all cells in their bodies. Gutmann’s team therefore hypothesized that genetic abnormalities in brain cells surrounding astrocytes might be essential for tumor formation.

To test this theory, the team developed mice with no functional copies of the Nf1 gene in their astrocytes and only one functional copy in all other brain cells, a scenario identical to that of humans with the disease. Every mouse developed astrocyte tumors along the optic nerve or chiasm within the first 10 months.

According to Gutmann, understanding the events that lead to tumor growth is critical for learning how to predict -- and hopefully prevent -- tumors.

"It’s clear from our findings that tumors do not form simply by losing both copies of the Nf1 gene," he explains. "If we figure out what external cues are necessary to trigger tumor growth, we could try to shut off that switch and stop tumors dead in their tracks without having to correct the underlying genetic defect."

The potential for the mouse model used in this study to serve as a preclinical model of NF1 is enhanced by the team’s ability to detect tumors in their very early stages using a powerful 4.7-Tesla magnetic resonance imaging (MRI) scanner and algorithms developed by Gutmann’s colleagues at the Mallinckrodt Institute of Radiology at the School of Medicine. Their techniques and equipment enable them to detect tumors the size of a piece of thread.

"We’re now beginning to detect these tumors even earlier using MRI," Gutmann says. "I think we’ve gotten to the point where this mouse model can not only help us understand more about the cell biology underlying brain tumor development, but also provides a tool for developing and evaluating better treatments."


###
Bajenaru ML, Hernandez MR, Perry A, Zhu Y, Parada LF, Garbow JR, Gutmann DH. Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity. Cancer Research, vol. 63, pp. 8573-77, Dec. 15, 2003.

Funding from the National Institutes of Health, the Small Animal Imaging Resource Program, the United States Army Medical Research and Material Command’s Office of Congressionally Directed Medical Research Programs and the National Neurofibromatosis Foundation supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Gila Z. Reckess | EurekAlert!
Further information:
http://medinfo.wustl.edu/

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>