Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover brain tumor's 'grow-or-go' switch

12.03.2010
Cancer cells in rapidly growing brain tumors must adjust to periods of low energy or die. When energy levels are high, tumor cells grow and proliferate. When levels are low, the cells grow less and migrate more.

Researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute have discovered the switch responsible for this grow-or-go behavior.

Their study shows that a molecule called miR-451 coordinates the change, and that the change is accompanied by slower cell proliferation and an increase in cell migration.

This behavior was closely linked to the cancer's ability to invade and spread. For this reason the molecule might serve as a biomarker to predict how long patients with the brain tumor glioblastoma multiforme will survive and may serve as a target to develop drugs to fight these tumors.

The researchers found that glioblastoma cells shift from their typical means of metabolizing glucose – a sugar brought by the bloodstream and usually used for energy – to an alternate means that consumes resources within the cell.

The findings are published in the March 12 issue of the journal Molecular Cell. "

Our study reveals how brain tumor cells adapt to their surroundings and survive conditions that might fatally starve them of energy," says co-author Dr. E. Antonio Chiocca, professor and chair of Neurological Surgery at Ohio State. "We have discovered that glioblastoma cells use miR451 to sense the availability of a nutrient – glucose.

"Levels of miR-451 directly shut down the engine of the tumor cell if there in no glucose or rev it up if there is lots of glucose. This important insight suggests that this molecule might be useful as a biomarker to predict a glioblastoma patient's prognosis, and that it might be used as a target to develop drugs to fight these tumors."

About 10,000 new cases of glioblastoma multiforme occur annually in the United States. The tumors are highly invasive, which makes them difficult to remove surgically, and respond poorly to radiation therapy and chemotherapy.

Average survival is 14 months after diagnosis.

MiR-451 belongs to a class of molecules called microRNA, which play a key role in regulating the levels of proteins that cells make. Changes in levels of these molecules are a feature of many cancers, the researchers say.

"The change in miR-451 expression enabled the cells to survive periods of stress caused by low glucose, and it causes them to move, perhaps enabling them to find a better glucose supply," says principal investigator Sean Lawler, assistant professor of neurological surgery.

"The migration of cancer cells from the primary tumor, either as single cells or as chains of cells, into the surrounding brain is a real problem with these tumors. By targeting miR-451, we might limit the tumor's spread and extend a patient's life."

For this study, Lawler, Chiocca, Jakub Godlewski, the postdoctoral fellow who was the first author of the study, and their colleagues first compared microRNA levels in migrating and nonmigrating human glioblastoma multiforme cells. The analysis suggested an important role for miR-451.

Experiments with living cells showed that high levels of glucose correlated with high levels of the molecule, and that this promotes a high rate of tumor-cell proliferation. Low glucose levels, on the other hand, slowed cell proliferation and increased cell migration.

Furthermore, when the researchers boosted levels of the molecule in migrating cells, it slowed migration 60 percent, and, after 72 hours, nearly doubled the rate of cell proliferation compared with controls.

Most exciting, when they forced an increase in miR-451 levels, the cells quickly died, suggesting a possible role in therapy.

Analyses of patient tumors showed that three of five had elevated levels of the molecule. Finally, the researchers compared the survival in 16 patients with high miR-451 and 23 patients with low levels. Those with high levels of the molecule had an average survival of about 280 days while those with low levels lived an average of about 480 days.

"This suggests that molecule may be a useful prognostic marker," Chiocca says.

Funding from the Esther L. Dardinger Endowment for Neurooncology and Neurosciences, the American Brain Tumor Association, and The Jeffrey Thomas Hayden Foundation Postdoctoral Fellowship supported this research.

Other Ohio State researchers involved in this study were Michal O. Nowicki, Agnieszka Bronisz, Gerard Nuovo, Jeff Palatini, Michael De Lay, James Van Brocklyn and Michael C. Ostrowski.

The Ohio State University Comprehensive Cancer Center- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top 20 cancer hospitals in the nation, The James (cancer.osu.edu) is the 180-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven funded programs in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.

Darrell E. Ward | EurekAlert!
Further information:
http://www.osumc.edu

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | 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

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>