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    Richard J. Gilbertson, MD, PhD

    Discovery may mean better ependymoma treatments

    Brain tumors called ependymomas that occur in different parts of the central nervous system appear to arise from different subpopulations of stem cells called radial glia cells (RGCs), according to investigators at St. Jude Children’s Research Hospital. The discovery explains why some identical-looking ependymomas are actually distinctly different diseases, the researchers said.

    This new information, in combination with techniques used to conduct the study, holds promise for designing more effective treatments for ependymomas as well as for other solid tumors. A report on this work appears in the October 2005 issue of Cancer Cell.

    RGCs are unspecialized cells that line the surface of the ventricles (fluid-filled spaces in the brain) and the spinal cord, and give rise to normal mature cells in the nervous system. By comparing the gene expression patterns in human ependymomas with those in the normal developing mouse nervous system, the St. Jude investigators were able to pinpoint RGCs as the cells from which ependymomas are likely to arise.

    The finding is consistent with evidence that cancers arise from, and are maintained by, a rare number of mutated stem cells called cancer stem cells, according to Richard Gilbertson, MD, PhD, St. Jude Developmental Neurobiology. Gilbertson is senior author of the Cancer Cell paper.

     “Our demonstration that identical-looking ependymomas that arise in different regions of the central nervous system are distinct diseases because they arise from different stem cells is an important insight,” he said. “This suggests that treatments should be designed to kill the underlying cancer stem cell population. If you kill only the cells making up the bulk of the tumor, the disease will likely return, because you haven’t eliminated the source of the tumor. Further, our comparative analysis of malignant and normal developing tissues provides a new method of mapping stem cells of solid tumors.”

    The technique the St. Jude team used to identify populations of RGCs as cells of origin of ependymoma could also be used to identify new treatments of ependymoma, according to Helen Poppleton, PhD, St. Jude Developmental Neurobiology. “Designing drugs that kill the malignant RGC could identify a whole new treatment for this disease,” she said. Poppleton, one of the paper’s authors, did much of the work on this project.

     

    Last update: November 2005