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Researchers discover brain tumor's 'grow-or-go' switch
Date:3/11/2010

ly 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 resea
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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

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