Photo: Brain Tumour Research

Researchers from the University of Portsmouth’s Brain Tumour Research Centre of Excellence have identified molecules that are responsible for metastatic lung cancer cells binding to blood vessels in the brain.

In order for a cancer cell to enter the brain, it must first bind to the cells that line the structure separating the blood from the brain, which is called the blood-brain barrier (BBB). Such information about the factors associated with this process may provide a way of preventing the cancer cells binding to the BBB and crossing over into the brain.

Twenty to 40 percent of patients with non-small cell lung cancer (NSCLC) develop brain metastasis.

The study, funded by the charity Brain Tumour Research and conducted by researchers at their UK Centre of Excellence at the University of Portsmouth, examined the factors present on the surface of NSCLC cells. These cells have different factors on their surfaces that determines how “sticky” the cells are and whether they are responsible for mediating the cancer cells binding to the blood vessel walls.

One of these factors is a molecule called CD15s. While it is present on a number of different types of cells in the body, it is expressed at higher levels on metastatic tumor cells, including those which have spread from the lung. It is only present at low levels in lung cancer cells that are not metastatic and remain within the lung.

The scientists examined what CD15s binds to on the blood vessel wall and identified another factor called CD62E. The researchers then used a specific tool to block the CD15s on the surface of the tumor cells, and this prevented the NSCLC cells from attaching to the blood vessels. They also used a model that simulated the cancer cells flowing through the blood vessels, and got the same result. So, blocking the adhesive properties of CD15s may provide a tool to prevent the establishment of secondary cancers.

“Although this work is still at an early stage, we have demonstrated key elements that are associated with tumor cell binding to blood vessels and this may provide a target for future drug development to prevent the development of secondary tumors in the brain. Increasing our understanding of the adhesive properties of tumors may also help to develop new treatments to halt the development and spread of primary brain tumors,” said Geoff Pilkington, study co-author and Head of the Brain Tumour Research Centre.

The adhesive properties of cancer cells play a key role in the formation and development of a tumor. While cells in a low-grade tumor bind very tightly together, the cells become less adhesive as the tumor becomes malignant. This is very important for the tumor cells that then spread into the surrounding nervous tissue. Understanding more about the factors that mediate cell adhesion is key for the potential identification of new therapies.

“Brain tumors kill more children and adults under the age of 40 than any other cancer, yet just one percent of the national spend on cancer research has been allocated to this devastating disease," said Kieran Breen, director of research at Brain Tumour Research. We are funding vital research in the UK to address this situation and are encouraged by Professor Pilkington’s findings.”

In addition to primary tumors, which start in the brain, the secondary or ‘metastatic’ tumors originate elsewhere and migrate to the brain have been the focus of this new study. Secondary brain tumors are most likely to originate in the breast, lung or skin (melanoma). When they enter the brain, they generally form multiple tumors and can be extremely difficult to treat. Usually, treatment would require whole-brain radiation, which is extremely toxic and the average survival time is just three to six months from diagnosis, with fewer than 20 percent of patients surviving more than one year. If the people whose tumors are more likely to spread to the brain could be identified, researchers may be able to prevent this from happening.