A group of scientists have succeeded in identifying three genes that specifically mediate the metastasis (spread) of breast cancer to the brain and how.
Researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) have found that COX2 and HB-EGF - genes that induce cancer cell mobility and invasiveness - are the genetic mediators in the spread of breast cancer to the brain.
They say that a third gene, ST6GALNAC5, has been found 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," Nature magazine quoted Dr. Joan Massague as saying.
Typically, breast cancer metastasis to the brain occurs years after removal of a breast tumour, 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.
Thus, in order to generate brain metastasis, circulating cancer cells need to pass through the blood-brain barrier and interact with the brain microenvironment.
For the study, researchers isolated cancer cells that preferentially targeted the brain from patients with advanced disease.
On 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.
They found that ST6GALNAC5, an enzyme that is normally active only in brain tissue, causes a chemical reaction that creates a coating on the surface of breast cancer cells that enhances their ability to breach the blood-brain barrier.
The researchers also noted that COX2 and HB-EGF, which prime breast cancer cells for entrance into the brain, had previously been found to be involved in breast cancer's spread to the lung.
This indicated a partial sharing of genetic mediators of metastasis to both the brain and lung and may explain the association of brain and lung relapse in women with breast cancer.