Funded Research

February 15, 2008: The Liddy Shriver Sarcoma Initiative is funding a $37,800 research study, Identification of the Ewing’s Sarcoma Stem Cell, at the Sidney Kimmel Comprehensive Cancer Canter at Johns Hopkins Medical School. The funding of this grant is made possible by a generous gift from the Arlo and Susan Ellison family to the Liddy Shriver Sarcoma Initiative, by family and friends to honor the memory of Christie Campbell, Jeremy Zimmer, Brad Rice, Peter Skelton, and Paul Onvlee who all fell victim to this disease, and by family and friends to honor Teri Marriage, Matthew Beaver, and Nick Gibboni who are all still fighting it. Donations were also received in memory of Jeremy's grandfather, Robert Pickrell.

This study is led by David M. Loeb, M.D., Ph.D. who is Director of the Musculoskeletal Tumor Program and Co-Director of the Sarcoma Program. Dr. Loeb will be joined by Saul J. Sharkis, PhD, Professor of Oncology and Medicine, Chi Van Dang, M.D., Ph.D., Professor of Cell Biology and Jason T. Yustein, M.D., Ph.D., a fellow in the Pediatric Hematology-Oncology program. This team hopes to demonstrate the existence of Ewing’s sarcoma stem cells and then to begin the functional characterization of these cells. The following is taken from the abstract of the grant application:

The cancer stem cell (CSC) model predicts that there is a small subpopulation of "stem cells" within each tumor that is responsible for tumor self-renewal, generation of the bulk of the tumor cells, and causing relapse. CSCs have been identified in brain tumors, breast cancer, and leukemia. It is not known whether Ewing’s sarcoma (EWS) stem cells exist. The aims of this proposal are 1) to demonstrate the existence of EWS stem cells (ESSC) and 2) to begin the functional characterization of these cells. We will use EWS cell lines, and these will be analyzed using 3 different assays, both singly and in combination: 1) exclusion of the DNA binding dye Hoechst 33342, 2) high level expression of aldehyde dehydrogenase, and 3) ability to form spherical colonies in nonadherent culture conditions. The combinatorial application of these assays to a single cell population is a novel approach that has not been reported before. We will also evaluate several EWS xenografts to confirm the presence of these cells in a second model system. Putative ESSCs will then be injected into immunodeficient mice to evaluate their tumorigenicity and self-renewal, the hallmarks of CSCs. Upon successful completion of this study, we will have demonstrated the existence of ESSCs in both EWS cell lines and in xenograft models and will have begun the initial functional characterization of these critical cells. Future work will then confirm that ESSCs are found in primary EWS samples, will perform more detailed analysis of the biology of these cells (including identification of the cell of origin of Ewing’s sarcoma and assessing the potential of ESSCs for differentiation), and will eventually lead to the development of therapies targeted at the cells that are responsible for disease relapse and patient death. Such therapies are expected to profoundly impact the course of EWS, especially for patients with metastatic disease at the time of diagnosis, whose prognosis has not changed over the past 40 years.

You can read more about the approach they are taking in this study in Dr. Loeb’s article, Identification and Characterization of the Ewing’s Sarcoma Stem Cell, which appears in the February 2008 issue of ESUN.