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Tumor cells that border normal tissue are told to leave

he study demonstrated that it was the difference in Src activity that led to the change in the attachment proteins. When a high Src cell (tumor cell) was next to a low Src cell (normal cell) the attachment proteins changed their characteristics, and the high Src cell became "unglued."

In addition, this change sent a signal that activated several other proteins in the tumor cell, one of which was an enzyme that dissolves the matrix surrounding cells. This enzyme makes it possible for a cell to move through tissues.

"Even though all the cells in the tumors we created were genetically identical, the proximity of the boundary cells to normal cells--their interaction with normal cells--made them special," Vidal says. "This is the first time the epithelial environment has been shown to play a role in metastasis."

The cells that left the fruit fly tumors eventually succumbed to the natural process of programmed cell death and were eliminated. According to Cagan, that was not unexpected.

"In a tumor, probably 99.99 percent of the border cells are raining out of the edges and dying," Cagan says. "But as oncologists have found, cancer stems from an accumulation of genetic mutations. If one of these wandering cells acquires a second mutation that prevents cell death, it could go on to establish a metastatic tumor."

Having created a model for studying metastasis of tumor cells, the research team has begun to look for ways to manipulate boundary cells to prevent their metastatic behavior. They have seen that disabling some of the genes in the pathway activated in boundary cells stops the cells from leaving the tumor.

Cagan's laboratory also has developed a robotic system for screening anticancer drugs, and they plan to use this system to look for drugs that will affect the metastatic process in their fruit fly model.

"A drug that can prevent metastasis would be an important adjunct for cancer treatments," Cagan says. "It co
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Source:Washington University School of Medicine


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