New research led by investigators at Memorial Sloan-Kettering Cancer Center (MSKCC) identifies three genes that specifically mediate the metastasis, or spread, of breast cancer to the brain and illuminates the mechanisms by which this spread occurs. The study was published online today in Nature.
According to the study, COX2 and HB-EGF - genes that induce cancer cell mobility and invasiveness - were found to be genetic mediators in the spread of breast cancer to the brain. A third gene, ST6GALNAC5, was shown to provide cancer cells with the capability of exiting the blood circulation and passing through the blood-brain barrier to enter the brain tissue.
"Our research sheds light on the role these genes play in determining how breast tumor cells break free and, once mobile, how they decide where to attack," said Joan Massagué, PhD, Chair of the Cancer Biology and Genetics Program at MSKCC and a Howard Hughes Medical Institute investigator.
Breast cancer metastasis to the brain typically occurs years after removal of a breast tumor, suggesting that disseminated cancer cells initially lack the specialized functions needed to overtake the dense network of capillaries that constitute the blood-brain barrier. This barrier prevents the entry of circulating cells and regulates the transport of molecules into the brain tissue. To generate brain metastasis, circulating cancer cells must, therefore, be able to pass through the blood-brain barrier and interact with the brain microenvironment.
In the study, Dr. Massagué and his colleagues isolated cancer cells that preferentially targeted the brain from patients with advanced disease. By combining this approach with gene expression profiling, additional testing in mouse model systems, and analysis of a body of clinical data, the investigators identified certain genes and functions that selectively mediate cancer cell passage through the blood-brain barrier.