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Breast cancer cells pose as neurons to invade the brain

— 2014-01-11

Breast cancer impersonates neurons to invade the brain

Breast cancer cells can spread undetected in the brain by masquerading as neurons and hijacking their energy supply. The resulting tumours can be devastating, and frequently strike breast cancer survivors after they’ve enjoyed many years of remission.

breast-cancer-cell

For every tumour that originates in the brain, 10 arrive there from other organ systems. Understanding how tumours spread, or metastasise, and survive in the brain is important because the survival rate of people with brain metastases is poor – only a fifth are still alive a year after being diagnosed.

So Rahul Jandial, a neurosurgeon at the City of Hope Cancer Center in Duarte, California, decided to explore how breast cancer cells are able to cross the blood-brain barrier to enter the brain and how they then avoid destruction by the immune system. He and his team wondered whether the tumour cells that survived were the ones that could somehow use the chemicals in the brain, such as neurotransmitters, in the same ways that neurons do.

To test the idea, they sampled metastatic breast cancer cells in the brains of several women and grew them in the lab. They compared the expression of proteins involved in detecting and absorbing a neurotransmitter called GABA in these cells with what happens in non-metastatic breast cancer cells. Neurons can use GABA to make energy.

Only the breast cancer cells taken from the brain expressed a receptor for GABA, plus a transporter protein to bring it into the cell and a host of other compounds that convert GABA into energy. This suggests that the metastatic tumour cells had worked out a way to disguise themselves as neurons, allowing them to thrive and hide from the immune system (PNAS, doi.org/qrr).

“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. “I think this is likely a tremendous advance in breast cancer research.”

But understanding the disguise requires further work. For example, it’s not clear whether breast cancer cells evolved the GABA machinery by chance over time, or whether they somehow acquired it from their environment.

Jandial hopes the results will lead to chemotherapies based on existing drugs for brain cancers or neurodegenerative disease, or novel drugs to treat tumours that spread to the brain. By Alyssa Botelho.

breast-cancer-tumor
Fig. 1.
A 47-y-old female with breast cancer metastasis to the brain. (Lower) Preoperative T1 gadolinium-enhanced magnetic resonance imaging and 3D reconstruction on a 3-T magnet scanner shows a left parietal lobe brain tumor (*). (Upper) After surgical resection, a specimen incorporating the tumor/brain boundary (perforated white line) was stained, and 3D rendering demonstrates hypertrophic GFAP+ reactive astrocytes (red) and HER2+ breast cancer cells (green). Nuclear DNA is counterstained with DAPI (blue) (40× magnification).

Source : Journal reference: PNAS, DOI: 10.1073/pnas.1322098111 
         Magazine NewScientist Jan 2014

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