Cancer Cells Signal Before They Migrate

Why tumor cells migrate to one organ and not another has long confounded cancer researchers. But a new study may provide a critical break by showing that cancer cells contain genetic signatures that indicate whether--and where--they're likely to move.

Cancer biologist Joan Massagué of the Memorial Sloan-Kettering Cancer Center in New York City uncovered the new clues by studying breast cancer metastasis, in which malignant cells tend to spread to the bones and lungs. Massagué and colleagues took cells from a single patient, injected them into mice, and isolated the cells that spread and thrived in the lungs. Analysis of the most aggressive of these cells revealed a pattern of gene expression distinct from that known to occur in breast-to-bone metastasis, as described in an earlier paper by Massagué. The team also found that these genes had different functions in promoting metastasis: One group encouraged growth of tumor cells in both breast and lungs, whereas the other only helped the new tumor thrive in the lungs.

To test the accuracy of this genetic warning, the researchers took 5-year-old tissue samples from 82 breast cancer patients. Based on the mouse findings, the team classified the patients as high or low risk for lung metastasis. Of those that had the high-risk signature, cancer spread to the lungs in 55%, in spite of chemotherapy treatment, whereas only 10% of the others showed cancer migration to the lungs--and even then, the lungs were not the principal or most aggressive site, the team reports 28 July in Nature.

With additional information on the functions of these genes, "one could predict a risk of relapse metastasis disease showing up years later and the site at which it would come back," says Massagué. In addition to improved prognostic ability, he says, doctors could adapt patient care to an individual, determining whether more or less aggressive interventions are needed.

"It's a very nice, complete paper," says Ann Chambers, a tumor biologist at the University of Western Ontario in London, who studies the mechanisms of metastasis. Gene signatures have generally been studied only as markers of poor prognoses, she says. "[Massagué has] added functionality--how the genes work to contribute to metastasis--and then he put those genes to a clinical test. I think it opens up a number of areas for research."

Related sites
Massagué's lab Web site
Chambers's lab Web site
The National Cancer Institute