One of the most exciting trends in cancer research is the new focus on stem cells.  No, not the embryonic stem cells that have ethicists debating the merits of cells that are obtained from a human embryo, but cancer stem cells.  When I was in medical school, we were taught that every cell in a tumor was the same, and all of them were capable of limitless growth and of spreading from the primary tumor. 

It turns out that that is probably not true. 

Many tumors seem to be made up of a large bulk population and a small subpopulation of cells with many characteristics of stem cells.  These so-called cancer stem cells are resistant to chemotherapy, can proliferate indefinitely, and can produce not only the bulk of a tumor but also more of themselves (a process called self renewal).

 Does Ewing’s sarcoma have stem cells?  No one knows for sure, but a group of scientists in France conducted experiments that appear to say "yes".  As many of you know, Ewing’s sarcoma is characterized by a chromosome translocation that results in the production of a protein called EWS/Fli1.  EWS/Fli1 is found in Ewing’s sarcoma but no other cell types, and is thought to be the major cause of Ewing’s sarcoma.  The French scientists came up with a way of turning off EWS/Fli1 in Ewing’s sarcoma cells in the lab.  They then examined all of the genes that were active in the Ewing’s sarcoma cells before and after turning off EWS/Fli1.  They compared these "gene expression profiles" with the profiles of other cells, and found that the gene expression profile of Ewing’s sarcoma cells with EWS/Fli1 turned off bears a striking resemblance to the gene expression profile of a cell type called mesenchymal stem cells.

What does this mean?  I think it means a couple of things.  First of all, it suggests that possibility that Ewing’s sarcoma arises from mesenchymal stem cells.  The cell of origin of Ewing’s sarcoma has remained a mystery since Dr. Ewing first described what he called "endothelioma of bone."  Research from the past decade has suggested several different possible "sources" for Ewing’s sarcoma, but none of the experiments were definitive.  Although the experiments the French scientists reported are not definitive either, the idea that Ewing’s sarcoma comes from a mesenchymal stem cell makes a lot of sense in the context of everything known about Ewing’s sarcoma biology.

In addition to shedding some light on the cell of origin of Ewing’s sarcoma, these results strengthen the idea that Ewing’s sarcoma stem cells exist.  This is because many of the genes that remained active in the cells that had EWS/Fli1 turned off were genes that are typically active in stem cells in general.  So even if the similarity to mesenchymal stem cells is a coincidence, this group’s data still supports the idea of Ewing’s sarcoma stem cells.

It will be exciting to follow this research as it unfolds.  If it turns out that Ewing’s sarcoma is a tumor of mesenchymal stem cells, this may lead to important new understanding of the biology of this cancer that might eventually alter how it is treated.  If it turns out that Ewing’s sarcoma contains stem cells, and if these stem cells are as important as we expect, future research will undoubtedly aim at developing therapies targeted at Ewing’s sarcoma stem cells, and these therapies will probably profoundly change not only how we treat this disease, but the outcomes for patients.

David Loeb, MD, PhD