US scientists identify genes involved in spread of breast cancer to brain

In collaboration with the Press Association

US scientists have shed new light on how breast cancer cells spread to the brain across the 'blood-brain barrier'.

The blood-brain barrier is a dense network of capillaries that regulates the movement of molecules and cells into the brain.

Publishing their findings in the journal Nature, the US team has identified the roles that three different genes play in the process, and say their work could lead to new drugs to stop cancer reaching the brain.

 

The researchers took tumour samples from patients with advanced breast cancer and implanted them into mice. They followed these cells as they migrated to the animals' brains.

They then collected samples of cancer cells from the brains of these animals, and looked at which genes were turned off or on inside them.

Comparing these findings with the cells that hadn't spread, the researchers found that two genes, COX2 and HB-EGF, seem to facilitate the cancer cells' spread through the bloodstream to the brain.

Crucially, they found that another gene, ST6GALNAC5, seems to be the key that allows the cancer cells to 'unlock' the protective blood-brain barrier and enter the brain.

ST6GALNAC5 was previously known to be turned on in brain cells. The researchers believe that, in cancer, this gene instructs cancer cells to make a special coating that allows them to travel across the blood-brain barrier.

Dr Joan Massague, chair of the Cancer Biology and Genetics Program at Memorial Sloan-Kettering Cancer Centre (MSKCC) and an investigator at the Howard Hughes Medical Institute, commented: "Our research sheds light on the role these genes play in determining how breast tumour cells break free and, once mobile, how they decide where to attack.

"Our results draw attention to the role of the cell surface coating as a previously unrecognised participant in brain metastasis and to the possibility of using drugs to disrupt its interactions."

Blocking the development of secondary brain cancers is important. In about one in ten patients whose breast cancer has spread, the cancer goes to the brain and the outlook for these patients can be poor.

Liz Baker, senior science information officer at Cancer Research UK, said: "While this work is at an early stage and was only carried out in mice, it could have important implications for breast cancer treatment in the future.

"Cancer spread is one of the most challenging aspects of the disease so we welcome this discovery."

Professor Sir David Lane, Cancer Research UK's chief scientist, said: "This is a very exciting study. This work shows us one way in which breast cancer cells can spread into the brain.

"The genes they've identified could become good targets for new drugs as well as some existing medicines, so they offer hope of being able to block this particular form of metastasis."

References

 Bos, P., Zhang, X., Nadal, C., Shu, W., Gomis, R., Nguyen, D., Minn, A., van de Vijver, M., Gerald, W., Foekens, J., & Massagué, J. (2009). Genes that mediate breast cancer metastasis to the brain Nature DOI: 10.1038/nature08021