Healthy neurons form surprising connections with aggressive brain cancer cells

In a collaborative study by the University of Bergen, Universität Heidelberg and Das Deutsche Krebsforschungszentrum in Germany, researchers discovered that cancer cells in the brain communicate with healthy brain cells in a different way than previously assumed.

We were surprised to learn that neurons form synapses with cancer cells, which we thought only healthy cells do."
Professor Hrvoje Miletic, Department of Biomedicine, University of Bergen

Disturbing signals

The job of synapses is to transmit signals between the cells, which tell them what to do. Previously, researchers have assumed that only healthy cells form such synapses to communicate with each other.

Researchers have known that cancer cells communicate with healthy neurons, but not how. Thanks to the neuroscience expertise at Heidelberg University and brain cancer models from UiB, researchers could see how neurons form synaptic connections with cancer cells, stimulating cancer growth.

"The new insight has allowed us to open a completely new field to understand malignant brain cancer and how to attack it. Controlled testing of anti-epileptic medicine is perhaps a possible new strategy," Miletic says.

Anti-epileptic medicine against brain cancer

In epilepsy, neurons overreact, transmitting a slew of uncontrolled electrical impulses. The new research shows that impulses from neurons are transmitted to cancer cells through synapses and transformed into signals in cancer cells that stimulate growth.

Brain tumor patients often have epilepsy and are periodically put on anti-epileptic medications, but quit taking them after the seizures stop. Consequently, a future controlled study of anti-epileptic drugs could show whether there is a therapeutic effect in brain tumor patients.

"If we have a better understanding of how microtubules and synapses are formed, the mechanisms behind this and the kind of messages sent between the cancer cells, then we can find out what impact this has on cancer development and treatment," says Hrvoje Miletic.

Facts:

• Researchers from the University of Bergen have participated in an international project with researchers, including the German cancer research center DKFZ and Heidelberg University.
• Hrvoje Miletic heads the Miletic Lab that conducts research on so-called microtubules, which are tubular extensions inside the cells. Malignant cancer cells in the brain use these microtubules to form a communications network in the brain.
• In 2018, the Norwegian Cancer Society gave NOK 4 million to research microtubules, the communications network of brain cancer.

The University of Bergen

Journal reference:

Venkataramani, V. et al. (2019) Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature. doi.org/10.1038/s41586-019-1564-x.