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

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The most deadly aspect of cancer is metastasis: its ability to spread to other parts of the body, including the brain. The so-called 'blood brain barrier', made up of a dense network of capillaries, forms a natural defence between the brain and the rest of the body, preventing foreign substances and cells from entering the brain from the general bloodstream. Some advanced cancers such as breast cancer manage to break this barrier and invade the brain years after the primary tumour has been removed, a phenomenon that has puzzled scientists up until now.

The team of scientists at the Memorial Sloan-Kettering Cancer Center in New York investigated cancer cells removed from patients whose breast cancers had spread. They injected the cells into mice and isolated the ones that could grow in the mouse brains.

Following genetic analysis of these cells, the researchers found three genes likely to be involved in the spread of breast cancer to the brain. Two of these genes, COX2 and HBEGF, were shown to increase cancer cell mobility and invasiveness, and have been previously implicated in the spread of breast cancer to the lung. The third gene, ST6GALNAC5, normally only active in brain tissue, was shown to aid the cells specifically in penetrating the blood brain barrier. It appears to do so by causing a chemical reaction which creates a coating on the cancer cells, helping them 'stick' to blood vessels in the brain, and thereby enhancing their ability to breach the barrier. Without ST6GALNAC5, the cells fail to enter the brain tissue.

Joan Massague, chair of the Cancer Biology and Genetic Program at the center, and a Howard Hughes Medical Institute investigator, led the study along with graduate student Paula Bos and colleagues. Massague said: 'Our research sheds light on the role these genes play in determining how breast cancer cells break free and, once mobile, how they decide where to attack'. He continues that the work also 'draws attention to the role of the cell surface coating as a previously unrecognised participant in brain metastasis'.

Professor Sir David Lane, Cancer Research UK's chief scientist, described the findings as 'very exciting'. He said that 'the genes they've identified could become good targets for new drugs' since they 'offer hope of being able to block this particular form of metastasis'. He explained: 'one of the reasons why cancer is so hard to treat unless we catch it early is because it spreads'. 

Reference

1. Bos PD, Zhang XH, et al. Genes that mediate breast cancer metastasis to the brain. Nature 2009; 459(7249):1005–1009. doi: 10.1038/nature08021

klíčová slova: blood-brain barrier, metastasis, breast cancer