Breast cancer cells masquerade as neurons, allowing them to hide from the immune system, cross the blood-brain barrier and begin to form ultimately-deadly brain tumours, researchers have found.
Treatment and ‘cure’ of breast cancer does not ensure that the disease won’t spread to the brain. Too often, sometimes years after an initial diagnosis and remission, breast cancer cells are discovered growing as new tumours within the brain and researcjers have found how this happens.
“The most dreaded location for cancer to spread is the brain,” said Rahul Jandial, MD, PhD, a City of Hope neurosurgeon who led the study, published in the Proceedings of the National Academy of Science.
“As we have become better at keeping cancer at bay with drugs such as Herceptin, women are fortunately living longer. In this hard-fought life extension, brain metastases are being unmasked as the next battleground for extending the lives of women with breast cancer.”
Jandial et al wanted to explore how breast cancer cells cross the blood-brain barrier without being destroyed by the immune system.
“If, by chance, a malignant breast cancer cell swimming in the bloodstream crossed into the brain, how would it survive in a completely new, foreign habitat?” Jandial asked. He and his team hypothesised that given that the brain is rich in many brain-specific types of chemicals and proteins, perhaps breast cancer cells exploit these resources by assuming similar properties.
These cancer cells could potentially deceive the immune system by blending in with the neurons, neurotransmitters, other types of proteins, cells and chemicals.
Taking samples from brain tumours resulting from breast cancer, the researchers found that the breast cancer cells were using the brain’s most abundant chemical as a fuel source. This chemical, GABA, is a neurotransmitter used for communication between neurons.
When compared to cells from non-metastatic breast cancer, the metastasised cells expressed a receptor for GABA, as well as for a protein that draws the transmitter into cells. This allowed the cancer cells to essentially masquerade as neurons.
“Breast cancer cells can be cellular chameleons, or masquerade as neurons, and spread to the brain,” Jandial said. He added that further study is required to better understand the mechanisms that allow the cancer cells to achieve this disguise. He hopes that ultimately, unmasking these disguised invaders will result in new therapies.