Washington: American researchers have discovered the brain tumour switch responsible for the ``grow-or-go`` phenomenon. Cancer cells in brain tumours have to adjust to periods of low energy or die. When energy levels are high, tumour cells grow and multiply but when levels are low, the cells grow less and migrate more.
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, according to the researchers. Principal investigator Sean Lawler, assistant professor of neurological surgery, said: "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. "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 the study, Lawler, Chiocca, Jakub Godlewski, the postdoctoral fellow who was the first author of the study, and their team 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 demonstrated 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, demonstrated cell proliferation and increased cell migration. Moreover, when the scientists boosted levels of the molecule in migrating cells, it slowed migration 60 percent, and, after 72 hours, almost doubled the rate of cell proliferation compared with controls. Interestingly, when they forced an increase in miR-451 levels, the cells quickly died, suggesting a possible role in therapy.
Analyses of patient tumours demonstrated 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. Chiocca said: "This suggests that molecule may be a useful prognostic marker." The findings of the study have appeared in the March 12 issue of the journal Molecular Cell. ANI