One reason cancer is so deadly is that cancer cells can break away from where they originated and spread disease throughout the body. Stopping metastasis is a major goal in cancer therapeutics. Researchers have now found a molecule that might be able to stop lung cancer from spreading to the brain. This molecule, CD15s, allows metastatic lung cancer cells to bind to blood vessels inside the brain, where they can get a foothold.
Cancerous cells cannot just enter the brain; they have to attach to cells of the blood-brain barrier – a protective sheath that keeps the brain separated from blood circulating in the body. Researchers at the University of Portsmouth's Brain Tumor Research Centre of Excellence wanted to know more about how this process is facilitated and to see if it could be disrupted. Their findings have been published in the International Journal of Molecular Sciences.
This work focused on non-small cell lung cancer (NSCLC); around 30 percent of people affected by NSCLC will go on to have brain metastasis. NSCLC cells have various features on their surface that can give them a sticky property, and can determine whether or not they will bind to other cells.
By closely investigating these features on the cells, the investigators found that the CD15s gene is highly expressed in metastatic tumor cells, including those disseminating from lung cancer. The gene is only expressed at low levels in lung cancer cells that stay in the lung and do not migrate.
When the scientists blocked CD15s from being expressed on the tumor cell surface, NSCLC cells could not attach to blood vessels. This work suggests that if the action of CD15s can be blocked, it may be possible to stop metastasis in the brain, and maybe in other 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," explained Geoff Pilkington, a co-author of the report and a Professor of Cellular & Molecular Neuro-Oncology. "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," he continued.
Adhesion is critically important in cancer; when cells are tightly bound during the development of low-grade tumors, as malignancy increases the cells become less adhesive. The cancerous cells are then free to migrate to other areas. Therapeutics would benefit from a complete understanding of cell adhesion in cancer.
"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. We are funding vital research in the UK to address this situation and are encouraged by Professor Pilkington's findings," commented Dr. Kieran Breen, the Director of Research at Brain Tumor Research.
Learn more about brain tumors from Professor Pilkington, the Head of the Brain Tumor Research Centre who is featured in the above video.