The scientists have identified a protein that breast, lung and other cancers use to promote their spread — or metastasis — to the brain. The research will now focus on the ways to predict, prevent and treat brain metastases which cause cancer deaths.
The protein, CEMIP prompts blood vessel and resident immune cells in the brain to produce inflammatory molecules, which in turn support the survival and progression of cancer cells to form brain tumours. In lab-dish and animal-model experiments, removing CEMIP greatly impeded this brain metastasis process. In tests on human patients’ breast and lung tumours, the researchers linked high CEMIP levels to a high risk of metastasis to the brain, the team said.
“Our findings suggest that blocking CEMIP could be a good strategy for preventing or treating brain metastasis, and that monitoring CEMIP levels in primary tumors might enable us, for the first time, to predict the risk of brain metastasis,” said co-senior author Dr. David Lyden, the Stavros S. Niarchos Professor in Pediatric Cardiology, and a professor of pediatrics and of cell and developmental biology at Weill Cornell Medicine.
The majority of cancer deaths are caused not by the initial, primary tumours that form but by secondary, metastatic tumours in vital organs. Brain metastases are the most lethal of these and are also relatively common, occurring in an estimated 150,000 to 200,000 cancer patients each year in the United States alone. There has been no good way to predict these metastases, let alone prevent or treat them.
The scientists found that CEMIP, a protein previously linked to some cancers, is produced at high levels by brain-metastasizing human breast and lung cancer cells. CEMIP is concentrated at especially high levels in these cells’ “exosomes,” tiny capsules that are secreted by cells and can circulate in the body and be taken up by other cells. In contrast, CEMIP tends to be produced at relatively low levels by cancer cells that metastasize to bones and other organs.
The scientists now are working with the Tri-Institutional Therapeutics Discovery Institute, a partnership including Weill Cornell Medicine, The Rockefeller University and Memorial Sloan Kettering Cancer Center, to develop a diagnostic test for CEMIP levels as well as a therapeutic antibody that in principle would delay or prevent brain metastasis by blocking CEMIP.