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By Hannah Hoag

Control Freaks

Tiny genetic snippets called microRNAs may promote metastasis

By Hannah Hoag


Biologists know quite a bit about the steps that turn a normal cell into a cancerous one. Their understanding of metastasis, on the other hand, is somewhat more hazy. Now a short stretch of genetic material has been implicated in the spread of breast cancer, according to a study in the Oct. 11 Nature.

Molecular biologist Li Ma of the Whitehead Institute for Biomedical Research, in Cambridge, Mass., has identified a type of microRNA—a tiny genetic molecule—that can coax breast cancer cells to spread to other tissues. MicroRNAs regulate the expression of genes by controlling the larger RNA molecules that help to make proteins.

Ma engineered non-metastatic breast cancer cells to overproduce a single microRNA, known as microRNA-10b, and injected the cells into the mammary fat pads of immune-deficient mice. The mice quickly developed breast tumors that spread to the lungs and the abdominal cavity.

“Some very specific steps of invasion and metastasis seem to be under the control of microRNA-10b,” says Robert Weinberg, a cancer biologist at the Whitehead, and one of the study’s authors. “It’s no longer the case that the whole process of invasion and metastasis is a black box.” Much of the process “can be explained by the actions of a relatively small number of genes and proteins.”

Ma carried her experiments further, finding factors that influence the levels of microRNA-10b, as well as its biological target. She identified a sequence of events in which high levels of a protein called Twist increase the production of microRNA-10b. This causes the activation of a pro-metastatic gene, which leads to tumor cell invasion and metastasis.

In breast cancer, a primary tumor is rarely a killer. “The problem is that it can come back in a different place in the body,” says molecular biologist Peter Jones, the director of the University of Southern California’s Norris Comprehensive Cancer Center, in Los Angeles. Many people who die of cancer die from metastases.

For a tumor to metastasize, it must complete a series of steps. The cancer begins by migrating into nearby tissue, and then it squeezes into the circulatory system, invades a new location and begins to grow.

“MicroRNAs are prime candidates for coordinating these complex gene-expression events that lead to metastasis,” writes Patricia Steeg, a cancer researcher at the National Cancer Institute, in an accompanying article in Nature.

Although scientists have been studying cancer for decades, microRNAs are a relatively new discovery. The first microRNA was discovered in 1993. Since then scientists have identified more than 200 microRNAs in humans and suspect there may be as many as 1,000 microRNAs that direct cell function.

“This is a very important area that will change the way we think about breast cancer and many other tumors,” says cancer researcher Carlo Croce, the director of the Human Cancer Genetics Program at the Ohio State University in Columbus. “It provides a new opportunity for diagnostic and prognostic markers, but also for treatment.”