Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Subtypes of ependymomas arise from rare stem cells in the nervous system

19.10.2005


Brain tumors called ependymomas that occur in different parts of the central nervous system appear to arise from subpopulations of stem cells called radial glia cells (RGCs), according to investigators at St. Jude Children’s Research Hospital. The discovery explains why some identical-looking ependymomas are actually distinctly different diseases, the researchers said.



This new information, in combination with the techniques used to conduct the study, holds promise for designing more effective treatments for ependymomas as well as for other solid tumors. A report on this work appears in the October issue of Cancer Cell. RGCs are unspecialized cells that line the surface of the ventricles (fluid-filled spaces in the brain) and the spinal cord, and give rise to normal mature cells in the nervous system. The St. Jude study found strong evidence that when rare populations of RGCs acquire mutations that disrupt the cell signaling pathways controlling growth and differentiation, these cells reproduce continually and give rise to an ependymoma.

The St. Jude finding that RGCs can give rise to these tumors is consistent with evidence from a variety of researchers that cancers arise from, and are maintained by, a rare number of mutated stem cells called cancer stem cells, according to Richard Gilbertson, M.D., Ph.D., associate member in the Developmental Neurobiology and the Hematology-Oncology departments. Gilbertson is senior author of the Cancer Cell paper.


The current discovery at St. Jude explains why ependymomas arising in various parts of the central nervous system are clinically different, even though they look the same histologically (as seen under a microscope), the St. Jude researcher said. For example, although all ependymomas look alike, supratentorial ependymomas arise in the top part of the brain in both adults and children; often cause weakness in the arms and legs, visual problems and seizures; and have a survival rate of 50-60 percent. Posterior fossa ependymomas arise in the back of the brain and cause patients to have an unsteady walk and neck pain; and they occur mainly in children and have a slightly worse prognosis than do surpratentorial tumors. A spinal ependymoma occurs mainly in adults, and more than 70 percent of patients who undergo surgery to remove this tumor survive.

"Historically, physicians based their diagnosis and treatment of cancer primarily on the histology of tumors," Gilbertson said. "So our demonstration that identical-looking ependymomas that arise in different regions of the central nervous system are distinct diseases at the cellular and molecular level is an important insight. This suggests that treatments should be designed to kill the cancer stem cells. If you kill only the cells making up the bulk of the tumor, the disease will likely return because you haven’t eliminated the stem cells that are the source of the tumor."

The St. Jude study is also important because ependymomas are the third most common central nervous system tumor in children and no effective chemotherapy exists for them. "If surgery and radiation doesn’t treat the entire tumor, then resistant stem cells left behind might re-grow the cancer," Gilbertson said. "And since children don’t tolerate radiation treatment well, we need new treatments that completely eliminate cells that produce the tumors."

The researchers made their discovery by first determining the patterns of gene expression in more than 100 tumor samples from patients with different types of ependymoma. Gene expression patterns, called signatures, reflect the specific genes that have been activated in the tumors. The signatures that distinguished supratentorial, posterior fossa and spinal ependymomas included genes that regulate the proliferation and differentiation of normal primitive cells in the corresponding region of the embryonic nervous system. For example, the St. Jude team showed that more than 80 percent of genes expressed at high levels in the supratentorial and spinal ependymomas are also expressed in the corresponding regions of the nervous system during development.

The team also demonstrated that each subtype of ependymoma contains rare populations of cells that resemble RGCs. Moreover, when these RGC-like ependymoma cancer stem cells were inserted into laboratory models that lacked protective immune systems, the stem cells formed tumors. This was additional strong evidence that mutated RGCs can give rise to ependymomas.

The different genetic signatures found in each subtype of ependymoma represent potential targets for new drugs designed to kill RGCs that give rise to each subtype of this tumor, said Gilbertson. Such individualized treatment might allow physicians to prevent the recurrence of ependymoma following treatment to remove the primary (original) tumor by eliminating the cancer stem cells that give rise to the tumor.

The technique the St. Jude team used to identify populations of RGCs as cells of origin of ependymoma could also be used to identify cancer stem cells for other solid tumors, according to Helen Poppleton, PhD, an associate scientist. "That new knowledge could lead to the development of new drugs that significantly improve the outcomes of a variety of cancers," Poppleton said. One of the authors of the paper, Poppleton did much of the work on this project.

Kelly Perry | EurekAlert!
Further information:
http://www.stjude.org

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>