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Tumor cells that border normal tissue are told to leave

The thin, single-cell boundary where a tumor meets normal tissue is the most dangerous part of a cancer according to a new study by scientists at Washington University School of Medicine in St. Louis. The researchers found that tumor cells bordering normal tissue receive signals that tell them to wander away from the tumor, allowing the cancer cells to establish deadly metastatic tumors elsewhere in the body.

The researchers say their discovery demonstrates the importance of the tumor's environment and shows more precisely how the metastatic process occurs and might be stopped. Their study appears in the January 10 issue of Developmental Cell.

"What actually kills in cancer is not the primary tumor--it's metastasis," says senior author Ross L. Cagan, Ph.D., associate professor of molecular biology and pharmacology and a researcher with the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital. "You can't study that in a laboratory dish. You have to look at the tumor cells in their natural environment--surrounded by normal tissues."

To do this, the research team created tumors in fruit fly eyes and wings that permitted them to study the behavior of individual tumor cells.

"We found that the tumor cells in direct contact with normal cells had a different behavior than cells further inside the tumor," says lead author Marcos Vidal, Ph.D., research associate in molecular biology and pharmacology. "They were exclusively the ones that tended to leave the tissue."

The tumors were generated by turning off an inhibitor of a major oncogene called Src (pronounced sarc), making the tumor cells high in Src oncogene activity. (An oncogene is a gene that increases the malignancy of a tumor cell.) This particular genetic change is common in human breast tumors.

Boundary tumor cells were shown to lose surface proteins that attach them to other cells and stabilize their position within tissues. The study demon
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Contact: Gwen Ericson
ericsong@wustl.edu
314-286-0141
Washington University School of Medicine
9-Jan-2006


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