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Newly discovered behavior in cancer cells signals dangerous metastasis

DURHAM, N.C. -- The most aggressively malignant cancer cells have a "toggle switch" that enables them to morph into highly mobile cells that invade other tissues and then nest comfortably in their new surroundings, a new study in rats suggests.

This picture of how cancer cells shift between two alternating states -- travelers and nesters -- represents a new understanding of how cancer metastasizes, or spreads to other parts of the body, said the Duke Comprehensive Cancer Center researchers who conducted the study.

"Understanding this toggle switch might ultimately enable scientists to find ways to stop cells from metastasizing, which is the most deadly trait of cancer," said the study's lead investigator, Mariano Garcia-Blanco, M.D., Ph.D., professor of molecular genetics and microbiology.

The researchers will publish their findings in the Sept. 19, 2006, issue of the journal Proceedings of the National Academy of Sciences, now available on line. The research was funded by the National Cancer Institute.

Until now, scientists have believed that cancer cells must transform permanently from stationary epithelial cells into migratory mesenchymal cells in order to metastasize.

The Duke team discovered that highly malignant cells are equal parts epithelial and mesenchymal, transitioning between the two as their surroundings necessitate. The proteins that the cell produces dictate which way the cell shifts.

In a classic example of survival of the fittest, a cancer cell's ability to toggle between epithelial and mesenchymal enables the most malignant cells to aggressively invade and then peacefully adapt in unfamiliar territory, the scientists said.

"The prevailing notion has been that the more mesenchymal the cancer cells, the more mobile and metastatic they would be," Garcia-Blanco said. "In reality, aggressive cancer cells are not homogenous, but are extremely versatile in their ability to adapt as their s
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Contact: Rebecca Levine
Levin005@mc.duke.edu
919-684-4148
Duke University Medical Center
15-Sep-2006


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