Research has shown for the first time how cancers that spread to the brain establish themselves and begin to grow.
The Oxford University study has identified the mechanism that metastatic cancer cells use to anchor themselves to blood vessels in the brain. This could allow new drugs to be developed to stop cancers from spreading and growing in the brain.
Metastasis is the process where cancer breaks out from where a tumor has initially grown and spreads to other parts of the body. It is usually the reason why cancer is fatal.
Brain metastases are the most common malignant tumors of the central nervous system, outnumbering by ten times those that originate in the brain. Once such cancers have reached the brain the prognosis is not good: the median survival is 9 months with maximal treatment. Over 20% of all cancer patients will eventually develop metastatic cancer in the central nervous system.
“Metastasis to the brain is essentially terminal, and very little is known about the process by which it occurs,” says lead author Dr. W Shawn Carbonell of the MRC/CRUK Gray Institute for Radiation Oncology and Biology at the University of Oxford and Brasenose College, Oxford. “But by quickly remedying our lack of knowledge, we hope to be able to come up with new and better ways of treating such cancers.”
The Oxford University team, with funding from Cancer Research UK, the Medical Research Council, and the US National Institutes of Health, set out to answer the question: how do tumor cells grow in the brain. They looked at a comprehensive range of cancer cell types from humans and mice – breast cancer cell lines, melanoma cells, and a lymphoma cell line – and examined how the cells establish themselves in the brain in laboratory studies, using both mice and human tissue samples.
Previously it had generally been assumed that tumor cells grew on the cells that make up the grey and white matter of the brain: the neurons and glial cells. However, no proper studies have been done before and there is little evidence to back this up one way or another.
Instead, the researchers found that the metastatic cancer cells start to grow on the walls of blood vessels in the brain in over 95% of cases, and not on the nerve cells. The researchers suggest that by ‘co-opting’ the vascular networks in the brain, the cancer cells can get all the nutrients and oxygen they need to start growing without having to grow new blood vessels of their own first.
The team also discovered that a particular protein called an integrin on the outside surface of the cancer cells is necessary for them to stick to the blood vessels. Removal of the integrin stopped the cancer cells from attaching and starting to grow. This discovery is promising, as it may be possible to develop drugs to target the integrin and stop brain metastasis.
“Although this research is a long way from coming up with a new treatment for those with brain metastases, these are exciting new findings,” says Dr. Carbonell. “We have identified the protein that cancer cells use to anchor themselves to blood vessels in the brain. Now we can try to come up with drugs to target this protein and stop metastatic cancer cells from taking hold in the brain.”
Illustration: Breast cancer cells (in green) grow only on blood vessels (red) in the brain of a mouse. –Shawn Carbonell.
University of Oxford News Release (06/10/09)
Science Daily (06/22/09)
Abstract (Public Library of Sciences ONE; 4(6) (06/10/09))