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

Blocking Cancer Stem Cells in the Brain Prolongs Survival in Mice

Published: Tuesday, May 27, 2014
Last Updated: Tuesday, May 27, 2014
Bookmark and Share
Blocking the stem cell marker slow down the growth of aggressive human brain cancers.

In a study of malignant brain tumors in mice, scientists from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have identified a key molecule that is responsible for the dangerous properties of tumor stem cells. When this stem cell marker was switched off, cancerous mice survived longer.

Switching off the marker in human brain tumor cells causes cancer stem cells to lose their capacity for self-renewal. Blocking the marker may therefore also slow down the growth of aggressive human brain cancers.

Cancer researchers believe that many types of cancer originate from stem cells that have undergone transformations. This theory has far-reaching implications for cancer therapies, which may only be effective over the long term if they eliminate the cells from which the disease originates. However, in many types of tumors, scientists have yet to identify markers that are typical of such stem cells.

"In order to specifically attack cancer stem cells, we first need to know the exact molecular structure that the therapy targets," says Dr. Haikun Liu from the DKFZ. "However, until now there has been no convincing evidence to suggest that cancer growth can be slowed down by turning off tumor stem cells."

Now for the first time, the DKFZ stem cell experts have been able to provide such evidence. Experiments with mice led to the identification of a protein called Tlx, which plays a key role in brain cancer stem cells. When the scientists switched off Tlx, cancer stem cells lost their ability to renew themselves, and animals with tumors survived longer.

Tlx is a so-called "nuclear receptor" that controls many genes involved in tumorigenesis. In previous studies, Liu had found that Tlx is important to the functions of normal neural stem cells. Higher-than-normal levels of Tlx promote the development of these neural stem cells into malignant brain tumors.

The brain tumors that Liu and his team studied in mice had properties resembling those of aggressive glioblastomas in humans. The researchers engineered the mice genetically that the tumor cells become green when Tlx gene is activated. Such cells constituted only a small portion of the total population of tumor cells. They divided slowly and, in cell cultures, grew into spherical structures called spheroids, which are considered a typical characteristic of stem cells. The fluorescent marker revealed that Tlx-positive cells can renew themselves and also generate “Tlx-negative” offspring. This means that the offspring have undergone a process of development, which is one of the defining features of stem cells.

Most interestingly, Dr. Liu and his team further engineered the model that allows them to switch off Tlx in fully established mouse glioblastomas, which is closely mimicking tumor therapy in clinic. Experiments in mice in which the scientists switched off the production of Tlx in the tumor stem cells promoted a longer survival of the animals. "Blocking Tlx reprograms the tumor stem cells toward a more non-malignant fate," Dr. Liu explains.

A look into the scientific literature suggested that the results were relevant beyond mice. In genome data collections of the U.S. TCGA Consortium, the scientists discovered that a high level of activity of the Tlx gene is associated with a particularly unfavorable prognosis.

Using cultured cells, Liu's team then turned off Tlx in various human glioblastoma stem cell lines. The cells lost their ability to form spheroids and could no longer be transferred from animal to animal in a continuous series. These are two classic methods to establish the properties of “stemness” in cells, which had now been lost in the glioblastomas.

"We have shown that the growth and survival of brain tumors are dependent on the tumor stem cells,” Dr. Liu summarizes. “We have identified Tlx as a target structure to be hit in these stem cells. We also now know that human glioblastoma cells depend on Tlx to maintain the properties of stem cells. Since blocking Tlx prolongs survival in mice, we assume that this may also be an effective strategy in slowing down the growth of aggressive brain cancer in humans.”

Tlx has further characteristics that make the scientist believe it will be a promising target for novel therapeutic approaches: The protein occurs only in cells of the central nervous system, where its inhibition is unlikely to lead to any severe side effects. Additionally, studies of other nuclear receptors have revealed that they make good targets for inhibition by therapeutic substances.


Further Information
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 2,500+ scientific posters on ePosters
  • More than 3,700+ 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.

Related Content

A Yardstick to Measure the Malignancy of Prostate Cancer
Researchers have been searching for regulatory proteins that change the epigenetic characteristics of prostate cancer cells.
Wednesday, December 10, 2014
Suspicions Confirmed: Common Cause for Brain Tumors in Children
An overactive signaling pathway is a common cause in cases of pilocytic astrocytoma, the most frequent type of brain cancer in children.
Tuesday, July 09, 2013
Life Technologies Partners with German Cancer Research Center to Create World-Class Genome Sequencing Facility
Life Technologies Corporation and the German Cancer Research Center (Deutsches Krebsforschungszentrum or DKFZ), today announced their collaboration to create the National High-Throughput Sequencing Center.
Thursday, June 03, 2010
Scientific News
Poor Survival Rates in Leukemia Linked to Persistent Genetic Mutations
For patients with an often-deadly form of leukemia, new research suggests that lingering cancer-related mutations – detected after initial treatment with chemotherapy – are associated with an increased risk of relapse and poor survival.
Searching Big Data Faster
Theoretical analysis could expand applications of accelerated searching in biology, other fields.
Growing Hepatitis C in the Lab
Recent discovery allows study of naturally occurring forms of hepatitis C virus (HCV) in the lab.
Inciting an Immune Attack on Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
Reprogramming Cancer Cells
Researchers on Mayo Clinic’s Florida campus have discovered a way to potentially reprogram cancer cells back to normalcy.
Genetic Overlapping in Multiple Autoimmune Diseases May Suggest Common Therapies
CHOP genomics expert leads analysis of genetic architecture, with eye on repurposing existing drugs.
Surprising Mechanism Behind Antibiotic-Resistant Bacteria Uncovered
Now, scientists at TSRI have discovered that the important human pathogen Staphylococcus aureus, develops resistance to this drug by “switching on” a previously uncharacterized set of genes.
How DNA ‘Proofreader’ Proteins Pick and Edit Their Reading Material
Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have discovered how two important proofreader proteins know where to look for errors during DNA replication and how they work together to signal the body’s repair mechanism.
Fat in the Family?
Study could lead to therapeutics that boost metabolism.
Tissue Bank Pays Dividends for Brain Cancer Research
Checking what’s in the bank – the Brisbane Breast Bank, that is – has paid dividends for UQ cancer researchers.
Skyscraper Banner

Skyscraper Banner
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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!