January 13, 2006

Research Reveals Secrets of Cancer’s Spread

Tumor cells on the periphery are the most deadly, study suggests

New research suggests that the most dangerous part of any cancer is the thin, single-cell boundary where a tumor meets healthy tissue.

Tumor cells that border normal tissue receive signals that instruct them to leave the tumor and travel through the body, resulting in the formation of deadly metastatic tumors in other locations, report researchers at Washington University School of Medicine in St. Louis.

The findings, which appear in the Jan. 10 issue of the journal Developmental Cell, demonstrate the importance of a tumor's environment. They also provide more information about the metastatic process and how it might be halted, the researchers said.

"What actually kills in cancer is not the primary tumor -- it's metastasis. 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," senior author Ross L. Cagan, associate professor of molecular biology and pharmacology, said in a prepared statement.

He and his colleagues created tumors in fruit fly eyes and wings and then observed the behavior of individual tumor cells in those settings.

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

The cancer cells that left the tumors in the fruit flies eventually succumbed to natural programmed cell death and were eliminated. This was not unusual.

"In a tumor, probably 99.9 percent of the border cells are raining out of the edges and dying," Cagan noted. "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."

The researchers are now investigating ways of preventing metastatic behavior in these tumor boundary cells.

More information

The U.S. National Cancer Institute has more about metastatic cancer.