St. Jude Children’s Research Hospital Release: Loss Of Caspase-8 Makes Neuroblastoma More Aggressive

MEMPHIS, Tenn., Jan. 5 /PRNewswire/ -- The caspase-8 gene plays a critical role in suppressing metastasis (spread) of neuroblastoma, and the expression of this gene is frequently absent in cancer cells that are aggressively metastasizing, according to investigators at St. Jude Children’s Research Hospital and the University of California at San Diego. Neuroblastoma is a tumor of the nervous system and is the most common tumor in infants younger than 1 year of age; it accounts for 7-10 percent of childhood cancers.

The investigators also showed in laboratory studies that restoring the expression of the caspase-8 gene suppressed neuroblastoma metastases.

The study’s findings are significant because they suggest that novel treatments that restore the tumor-suppression role of the caspase-8 gene might prevent the spread of neuroblastoma and improve patient outcome, according to Jill Lahti, PhD, Genetics and Tumor Cell Biology. Lahti is a senior author of a report on these findings that appears in the January 5 issue of the journal Nature.

Caspase-8 triggers apoptosis by binding to molecules called integrins that project from the surface of cells, including neuroblastoma cells. Normally, integrin molecules anchor the cell to the extracellular matrix-the material outside the cell consisting of gel and fibers that support and provide structure to tissues. When cells become dislodged from the extracellular matrix, as happens during metastasis, the unbound integrin molecules are free to bind with caspase-8, Lahti said. The binding of caspase-8 to integrin then triggers integrin-mediated death, a form of apoptosis.

The major part of this study was done by first co-authors, Tal Teitz (St. Jude) and Dwayne G. Stupack (UCSD). Other authors of this study include Matthew D. Potter and David Mikolon (UCSD), Peter J. Houghton and Vincent J. Kidd (St. Jude). This work was supported in part by the National Cancer Institute and ALSAC.

St. Jude Children’s Research Hospital

St. Jude Children’s Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization. For more information, please visit http://www.stjude.org.St. Jude Children’s Research Hospital
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