For the majority of patients, it is the metastasis (i.e. spread) of a cancer that is ultimately deadly. In the case breast cancers, patients can often enjoy several years in remission before being told that the cancer has in fact spread to their brain. Unfortunately this diagnosis often comes after it is too late for successful surgical removal to be guaranteed.
Although metastasis in general is a relatively common process, inevitably occurring during tumour progression, the brain is usually not suitable for tumour cells. The environment is very different from the rest of the body, and cells must pass through the protective blood brain barrier to get there. Despite this, for every tumour that originates in the brain, 10 arrive there from other organ systems.
In order to host tumours, either the brains physiological environment must change, or cancer cells themselves must adapt to the changing environment. It was with this in mind that Rahul Jandial, a neurosurgeon at the City of Hope Cancer Center in California, decided investigate rare patient matched samples of breast and brain tumours after surgical resection.
“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 says. He and his team wondered if breast cancer cells that could use the resources around them – neurotransmitters and other chemicals in the brain – would be the ones that survived and flourished. Jandial and his team hypothesised that to metastasise to the brain, breast cancer cells would acquire or express brain-like properties. Hence brain tumour samples should be subtly different genetically than their breast cancer parents.
Sure enough, they found that brain tumours showed a ‘GABAergic phenotype’ similar to that of other brain tissue. Unlike parent breast tumours, cells able to grow in the brain expressed a neurotransmitter (GABA) receptor, a transporter to bring GABA into the cell and a selection of other components to convert GABA into energy. Essentially these breast cancer cells were masquerading as neurons in order to hide from the immune system and take advantage of different sources of energy in the brain.
“The idea that metastasising cells can adopt a new identity, shielding them from intrinsic defence mechanisms, is very exciting and suggests that cancer cells are likely more plastic than previously suspected,” says Ellen Carpenter, a neuroscientist at the University of California, Los Angeles, who was not involved in the work. “I think this is likely a tremendous advance in breast cancer research.”
But understanding the neuronal disguise – a mechanism that other cancers may be using to spread in the brain, says Jandial – requires further work. For example, it’s not clear whether breast cancer cells evolved the GABA machinery by chance over time, or somehow acquired it from their environment. Still, Jandial hopes the results will lead to new chemotherapies based on existing drugs for brain cancers or neurodegenerative disease, or help us discover novel drugs to treat tumours that spread to the brain.
Journal reference: PNAS, DOI: 10.1073/pnas.1322098111