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Molecular Marker Identifies Normal Stem Cells as Intestinal Tumor Source
Date:12/17/2008

In addition to providing insights into the origins of cancer, the work might help scientists identify more effective treatments. "Normal stem cells are designed to withstand environmental insults," Gilbertson said. "Thus cancer stem cells might use these same mechanisms to resist chemotherapy and radiotherapy. Remnant cancer stem cells might therefore cause tumors to relapse and re-grow following treatment. If we could kill these cancer stem cells, we might be able to prevent relapse. Understanding the link between normal and cancerous stem cells should help us target the latter while preserving the former."

Working with mice, the researchers inserted a genetic switch that enabled them to selectively turn on a colored tracer molecule only in cells that were expressing, or had expressed, Prominin1. These tracer experiments revealed that Prominin1 cells generate the covering of the entire small intestine and are therefore the stem cell of this tissue.

Next, the researchers switched on cancer-producing machinery in the Prominin1 intestinal stem cells and used a fluorescent tracer to follow the offspring of these cells. Those studies revealed that the stem cells stopped making normal intestine and made tumors instead. "We saw a dramatic change in these laboratory models," Gilbertson said. "The tumorous tissue ultimately replaced the entire normal intestine. In terms of clinical importance, now that we have isolated both the normal, parental stem cells and the cancer stem cells, we can begin screening compounds that will affect the malignant stem cell but not the normal stem cell."

More broadly, Prominin1 might prove to be a useful marker to trace cancer stem cells in thekidney, brain, pancreas and other tissues. The researchers are also exploring the use of stem cell markers in diseases other than cancer. "As we develop these kinds of characteristic markers for stem cells, we might be able to
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SOURCE St. Jude Children's Research Hospital
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