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!
20.11.2017 | Washington University in St. Louis
Carefully crafted light pulses control neuron activity
20.11.2017 | University of Illinois at Urbana-Champaign
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
20.11.2017 | Earth Sciences
20.11.2017 | Earth Sciences
20.11.2017 | Life Sciences