MicroRNAs Keep Tumors in Place

By Jennifer Couzin
ScienceNOW Daily News
9 January 2008

When a cancer spreads, or metastasizes, it often becomes incurable. Now scientists are eyeing a new factor that may prompt tumor cells to start roaming: a deficit of molecules known as microRNAs, which modulate gene expression. Building on earlier work linking microRNAs to cancer, researchers have found that a lack of certain microRNAs encourages tumors to spread. They also report that in mice, the microRNAs can be manipulated to slow metastasis.

Metastasis is thought to occur for a host of reasons. Certain genes may be turned on or off in tumors, causing cells to jump ship; and some environments in the body are more hospitable to wandering cancer cells. Recently, scientists have begun to consider the role of microRNAs, which appear to be expressed at very low levels in tumors. That's led to speculation that when turned on, microRNAs can suppress tumors.

Joan Massagu%26eacute;, a cancer biologist at Memorial Sloan-Kettering Cancer Center in New York City, cast a wide net for disappearing microRNAs in breast cancers. He and his colleagues examined microRNA expression in cell lines from patients with aggressive breast cancer that had spread to bones or the lungs. They came up with six microRNAs whose expression was vanishingly low compared to normal tissue. The researchers injected mice with metastatic cells from a patient with breast cancer. When lesions formed in the bones or lungs of the animals, the team found very low expression of three of the six microRNAs.

Massagu%26eacute; and his colleagues also studied 368 banked tumor samples from breast cancer patients and looked at expression of the genes that are suppressed by the six key microRNAs; when gene expression is high, the microRNAs aren't active, and when it's low, they are. The researchers found that patients whose tumors expressed the genes had about a 50%26#37; chance of being alive and not having metastatic cancer after 10 years. Among those patients that were negative for all six genes--in other words, those whose microRNA expression was high and damping down gene expression--the number was about 75%26#37;, the team reports in the 10 January issue of Nature.

The team also investigated the impact of restoring expression of microRNAs in cancer cells injected into mice. Boosting expression of three of the six microRNAs before injecting the cancer cells dramatically reduced lung and bone metastases, although the mice still developed them eventually. "That was a very clean experiment," says Massagu%26eacute;. But "it's a far cry" from treating patients.

Laura van 't Veer, a molecular biologist at the Netherlands Cancer Institute in Amsterdam, agrees that clinical applications are far off, but she says the findings are promising. At the very least, microRNAs "may represent especially good indicators of metastasis" and could be used diagnostically, says Robert Weinberg, a cancer biologist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, whose group last year described a microRNA that plays a role in breast cancer metastasis (ScienceNOW, 26 September 2007). Massagu%26eacute; is now studying whether the microRNAs he came up with help prevent metastasis in other cancers.

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