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Boosting sarcoma cell death

Ewing sarcomas – rare, aggressive childhood cancers – are derived from mesenchymal cells in bone and soft tissues, and children with metastatic disease have poor survival.

In a search for new therapeutic options for Ewing sarcoma, Dai Chung, M.D., and colleagues tested a compound previously identified at Vanderbilt, ML327, that induces the expression of the cell adhesion protein E-cadherin. E-cadherin, a hallmark of epithelial cells, is often lost as cancer cells become invasive. Its re-expression in epithelial cancers blocks cell invasiveness.

Now, the investigators have demonstrated in Ewing sarcoma cells that ML327 increases E-cadherin and alters the expression of other proteins, consistent with a mesenchymal-to-epithelial transition in the cells. ML327 also increased cell death, and had additive effects with a cell death-inducing ligand called TRAIL that has been tested for Ewing sarcoma.

The findings, reported in the Sept. 16 issue of Biochemical and Biophysical Research Communications, support further study of ML327, both alone and in combination with TRAIL-based strategies, in the treatment of sarcomas.

This research was supported by grants from the National Institutes of Health (DK061470), American College of Surgeons Resident Research Scholarship, and Rally Foundation for Cancer Research.

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