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 Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Quantum material is promising 'ion conductor' for research, new technologies

17.08.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>