Great Debates: Metastasis Mystery

Why Does Cancer Spread—and How Can We Stop It?

By Troy Goodman

 

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By definition, cancer is a disease that spreads. But the definition of cancer spread—that is, metastasis—has been revised in recent years thanks to the research of UAB pathologist Danny Welch, Ph.D., a nationally recognized expert in the biology and genetics of cancer metastasis.

Even though metastasis is responsible for 90 percent of cancer deaths, it is the most poorly understood process in cancer biology, and one of the least studied, Welch says.

Scientists do know that tumors shed millions of cells into the bloodstream each day. These cells circulate through the body, seeking new tissue to colonize. The vast majority don’t survive in the turbulent bloodstream, or never find a suitable landing place.

But those that do survive start the deadly process all over again, multiplying rapidly to form new tumors. At least that was the conventional wisdom until seven years ago. That’s when Welch’s lab discovered several genes that could order cancer cells to stop metastasizing—and in the process made the old definition of metastasis obsolete.

These metastasis-suppressor genes—more than 20 have now been identified—work in unique and still mysterious ways. Each seems to specialize in certain types of cancer; the KISS1 gene, for example, suppresses melanoma, ovarian cancer, and breast cancer. The genes are present in cancer cells, but they are turned off. After Welch’s group discovered how to reactivate these suppressor genes, “we found that the cells still moved to other sites, but they just sat there as single cells,” he says.

More Than a Foothold

Using new technology, Welch’s lab was able to monitor these single cells and confirm that they remained dormant, no longer a threat to proliferate wildly. That meant that merely getting a foothold in new tissue is not enough for a cancer to have truly metastasized. Instead, Welch explains, cancer cells have to retain the power of uncontrolled growth to present a danger to patients.

Welch set about drafting a revised definition in light of these discoveries. “Metastasis is the spread of tumor cells to nearby or distant secondary sites where they will grow and establish a macroscopic secondary tumor,” he says, echoing the new definition. “The key word there is ‘macroscopic’—they grow to something you can see. Anything that is microscopic, while it’s not to be ignored, is not a bona fide metastasis.”

Welch’s lab continues to investigate metastasis-suppressor genes and look for ways to disable cancer cells throughout the body. All of this would not make cancer disappear, he notes, but keeping metastasis in check would be a major step forward. It would also let scientists rewrite the definition of metastasis yet again—transforming a lethal disease into a chronic but manageable condition.

 

More Information

Learn more about Danny Welch's metastasis research in this article from Crossroads, the magazine of the UAB Comprehensive Cancer Center.

 

UAB Department of Pathology

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