Researchers Uncover An Error In Immature Brain Cells

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In experiments done in lab and animal studies, a breakdown in proper cell development has been shown to cause brain-specific stem cells to become starter seeds for aggressive brain tumors called glioblastoma multiforme, according to research from a team of researchers at the National Cancer Institute (NCI) and the National Institute of Neurological Disease and Stroke (NINDS), parts of the National Institutes of Health (NIH).

This developmental breakdown is caused by an error in methylation, one of the cell's primary methods of controlling the extent to which genes are expressed. In laboratory studies and animal models of brain cancer, reversing this error repaired the breakdown, restoring the normal neural cell development pathway. The findings, which appear in the January 2008, issue of Cancer Cell, could increase basic understanding of brain tumor biology and lead to the development of targeted therapies for brain cancer.

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"The discovery of a link between tumor stem-like cells and expression control is both novel and exciting," said NCI Director John Niederhuber, M.D. "These results bring new clarity to how all aspects of the genome's function, regulation, and structure can be perturbed in the development of cancer."

Many researchers have come to believe that the activity of a small group of stem-like tumor starter cells, or tumor-initiating cells with stem-like properties (TICs) may be one of the main reasons that cancer develops. Like normal stem cells, TICs are able to self-renew; unlike stem cells , TICs give rise to cells that develop into tumors, instead of differentiating into normal tissue. TICs have been reportedly found in tumors in a number of organs, including the breast, colon, lung, and brain.

Because normal stem cells and TICs are similar in some ways and dissimilar in others, a research team led by Howard Fine, M.D., chief of the Neuro-Oncology Branch at NCI's Center for Cancer Research, set out to identify what biological pathways are altered in these starter cells that enable them to give rise to tumor cells. Harvesting TICs from glioblastoma multiforme patients, the Fine team developed a human cell called 0308 that did not respond normally to environmental cues

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