Three Genes Help Breast Cancer Spread to Brain

Three genes in mice may help explain how breast cancer cells overcome a natural barrier to get into the brain, scientists said Wednesday.

Two of the genes, COX2 and HB-EGF, have already been found to help cancer spread to the lungs, the team reported in the journal Nature.

The third — ST6GALNAC5 — appears to make the outer coat of cancer cells sticky, allowing them to linger in tiny blood vessels in the brain long enough to seep through and enter brain tissue.

"Our research sheds light on the role these genes play in determining how breast tumor cells break free and, once mobile, how they decide where to attack," Joan Massague of Memorial Sloan-Kettering Cancer Center in New York and a Howard Hughes Medical Institute investigator, who worked on the study, said in a statement.

When breast cancer spreads to the brain, it must pass through a dense network of capillaries that make up the so-called blood brain barrier.

This natural barrier helps keep toxins in the blood from reaching brain tissue. Some advanced cancers, however, manage to breach this barrier years after the original tumor was removed.

To study how this happens, Massague, graduate student Paula Bos and colleagues used cancer cells from patients whose breast cancer had spread. They injected them into mice, and isolated the ones that could grow in the mouse brain.

They also analyzed what genes in the mouse cells and in human cells were most active.

COX2 and HB-EGF appear to make cancer cells more mobile and more invasive, they found, while ST6GALNAC5 appears to cause a chemical reaction that coats the outside of breast cancer cells, making them sticky.

Massague said it may be possible to find drugs that can block this process.

Breast cancer is the top cancer killer of women globally. It is diagnosed in 1.2 million people every year and kills 500,000.