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!
World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
17.07.2018 | Information Technology
17.07.2018 | Materials Sciences
17.07.2018 | Power and Electrical Engineering