Specifically, he said, the candidate cells appear to be at an advanced stage of differentiation but are not yet mature astrocytes, a subcategory of glial cells. Astrocytes are comparatively large, star-shaped cells that influence the activity of neurons and provide structure for the cells of the brain.
The researchers also found that these astrocytic precursors expressed significant levels of a "chemokine receptor" called CXCR4. Chemokines are proteins that are produced and released by a variety of types of cells. Like chemical magnets, in a sense, they attract cells that have compatible receptors on their surfaces. When the proteins bind at the receptors, they activate internal signaling pathways that cause a cell to behave in a certain way.
CXCR4 is known to govern cellular migration and homing in a variety of cell types, including neuronal and glial precursors in the developing brain. The only known chemokine that binds with CXCR4 is stromal-cell derived factor-1 (SDF-1). High-grade gliomas have recently been found to secrete significant levels of SDF-1.
The authors conclude that SDF-1 secreted by glioma cells migrating away from a tumor attracts CXCR4 and the neural stem cells upon which these receptors reside. In fact, when these receptors were blocked from interacting with SDF-1 in the laboratory, neural stem cell migration toward glioma cells was inhibited, confirming the importance of the CXCR4/SDF-1 pathway.
"The identification of CXCR4 as a key element governing the process of neural precursor migration toward glioma cells may allow for more efficient isolation of potential tumor-tracking cells, which may hasten the therapeutic testing of glioma-tracking neural precursors in the clinical setting," said Dr. Black, who holds the Ruth and Lawrence Harvey Chair
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Contact: Sandra Van
sandy@vancommunications.com
1-800-880-2397
Cedars-Sinai Medical Center
4-May-2004