Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer stem cells linked to radiation resistance

23.10.2006
Certain types of brain cancer cells, called cancer stem cells, help brain tumors to buffer themselves against radiation treatment by activating a "repair switch" that enables them to continue to grow unchecked, researchers at Duke University Medical Center have found.

The researchers also identified a method that appears to block the cells' ability to activate the repair switch following radiation treatment. This finding may lead to the development of therapies for overcoming radiation resistance in brain cancer as well as other types of cancer, the researchers said.

Working with animal and cell culture models, the researchers found that a specific cellular process called the "DNA damage checkpoint response" appears to enable cancer stem cells to survive exposure to radiation and to switch on a signal to automatically repair any damage caused to their DNA.

"In recent years, people have hypothesized that cancer stem cells are responsible for the resistance of malignant tumors to radiation treatment," said Jeremy Rich, M.D., senior investigator of the study and an associate professor of neurology at Duke. "We have shown, for the first time, that this is indeed the case."

The findings appear Oct. 18, 2006, in the advance online edition of the journal Nature. The research was supported by the National Institutes of Health and a number of philanthropic organizations [complete list below].

The type of cancer that the researchers studied, glioblastoma, is highly resistant to radiation and other forms of treatment and is the most deadly form of brain cancer worldwide. Although aggressive treatments can destroy the majority of the cancerous cells, a small fraction of them remain and often regenerate into even larger masses of tumor cells.

Until recently, scientists knew little about what made these resistant cells different from those that succumb to radiation treatment. It was clear, however, that the cells shared characteristics similar to those of normally functioning nerve stem cells, Rich said.

In the current study, the researchers used glioblastoma tissue removed from patients during neurosurgery and created two separate models. For one model, the researchers extracted cells from the tissue and grew them in cultures in the laboratory. For the second model, they transplanted the glioblastoma tissue into the frontal lobes of the brains of mice.

The researchers first measured the number of glioma stem cells present in the original tissue and then administered set doses of ionizing radiation to the cell cultures and to the mice. In both cases, the researchers observed a roughly fourfold jump in the number of glioma stem cells present in the tumor tissue following radiation treatment.

Because ionizing radiation works primarily by causing permanent damage to the key genetic material of cells, DNA, the researchers hypothesized that the glioma stem cells survive and multiply by somehow fixing radiation-induced DNA damage better than the other cancer cells.

To test this, the researchers searched the tissue samples for specific proteins that are responsible for detecting DNA damage. Using cell samples taken from both study models, the team examined the DNA damage checkpoint response both before and after use of ionizing radiation treatments by testing for activation of the key proteins that detect DNA damage. The researchers wanted to know whether the cells, following exposure to radiation treatment, would repair the DNA damage by activating the checkpoint response or whether they would instead die.

The team found that after ionizing radiation, the DNA damage checkpoint proteins in glioma stem cells were more highly activated than in other cancer cells. This heightened activation, the researchers said, leads cancer stem cells to more effectively repair DNA damage and thus render the cells less likely to die as a result of the treatment.

In another set of experiments, the researchers treated both the test animals and the cell cultures with a drug, called debromohymenialdisine, which is known to inhibit the proteins involved in the activation process. They added the drug before and after radiation treatment and measured the number of surviving cancer stem cells.

They found that administering the drug before radiation did little to change the number of cancer stem cells, but giving the drug in conjunction with radiation appeared to halt the resistance of cancer stem cells to radiation. This finding, the researchers said, suggests that use of a checkpoint inhibitor during radiation ruins the cells' potential to repair themselves and increases the likelihood that the cells will die.

"Our findings show one pathway in cancer stem cells that promotes the radiation resistance of glioblastomas," said Rich. "Treatments that target DNA damage checkpoint response in cancer stem cells may overcome the radiation resistance and eventually allow us to help even greater numbers of cancer patients."

Tracey Koepke | EurekAlert!
Further information:
http://www.mc.duke.edu

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Supersensitive through quantum entanglement

28.06.2017 | Physics and Astronomy

X-ray photoelectron spectroscopy under real ambient pressure conditions

28.06.2017 | Physics and Astronomy

Mice provide insight into genetics of autism spectrum disorders

28.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>