Compound Targets, Destroys Cancer Stem Cells in Mice
THURSDAY Aug. 13, 2009 -- Researchers have identified a chemical able to seek out and destroy the stem cells that scientists believe give rise to cancer recurrence after treatment.
A growing body of research is showing that cancer stem cells play a role in cancer metastasis and in causing cancer to reappear even after treatment seems to have eradicated the initial tumor.
"Evidence is accumulating rapidly that cancer stem cells are responsible for the aggressive powers of many tumors," including breast, prostate, lung and others, said study author Robert Weinberg, a member of the Whitehead Institute for Biomedical Research at Massachusetts Institute of Technology.
Yet studying cancer stem cells in the lab has proven problematic. The cells, already fewer in number than other types of tumor cells, tend to lose their stem cell-like properties when grown outside the body.
In the study, which appears in the Aug. 13 online issue of Cell, researchers were able to generate large numbers of cancer cells with stem cell-like qualities through a technique called "epithelial-to-mesenchymal transition," which causes the cells to take on characteristics similar to stem cells.
"A critical aspect of our work was to generate relatively homogenous and stable populations of cancer stem-like cells that could then be used for screening," said co-lead study author Tamer Onder, a former graduate student at the Whitehead Institute for Biomedical Research and now postdoctoral research fellow at Children's Hospital in Boston. "We were able to achieve this by inducing the cancer cells into an epithelial-to-mesenchymal transition using novel reagents that we had developed in the lab."
Researchers then analyzed thousands of chemical compounds to determine which ones were effective in killing breast cancer stem cells.
They found that a chemical called salinomycin destroyed both lab-generated cancer stem cells, as well as naturally occurring ones. When compared to paclitaxel, a common breast cancer chemotherapy drug, salinomycin reduced the number of cancer stem cells by more than 100-fold and inhibited breast tumor regrowth in mice.
Researchers also looked at the effect of salinomycin on genes that previous research has implicated in very aggressive tumors. The study showed salinomycin decreased the activity of these genes, while paclitaxel didn't.
Additional research is needed to determine exactly how salinomycin works to kill cancer stem cells and if it will be as effective in humans as it was in mice, researchers said.
Posted: August 2009