Just like neurons, certain tumour cells possess synapses, according to three complementary studies published on 18 September in Nature (1–3). Synapses are structures that nerve cells use to communicate and it seems aggressive brain tumours may use these same connections to integrate and form networks throughout the brain – and to evade detection. These synaptic features were found not only in common brain tumours called gliomas but also in aggressive forms of breast cancer that spread to the brain.
Finding tumour cells that behave like neurons was a surprise to scientists and “unsettling”, Dr Michelle Monje, a paediatric neuro-oncologist at Stanford University in California told Nature. Nonetheless, the discovery provides supports an increasing awareness among researchers and doctors that the nervous system plays an important role in the growth of cancers. Monge and her colleagues discovered synapses between neurons and cells in paediatric gliomas (1).
Another team of researchers, led by Prof Frank Winkler, a neurologist at Heidelberg University in Germany, independently stumbled upon synapses in glioma samples taken from cancer cells and grown in the laboratory (2). The team also uncovered synaptic connections in human glioma tumours transplanted into mice as well as glioma samples from 10 patients. And these chemical synapses may be what allows tumour cells to grow and flourish.
Moreover, the findings help explain some of the bizarre characteristics of brain tumours, like the fact that they can weave themselves throughout the brain. Whereas other tumour types simply form a hard lump or mass. And this could also — at least in part — explain why brain tumours can often go undetected with few symptoms.
But not just the brain. In the third paper, scientists report that breast cancer cells can also act like neurons. This time, the team of researchers led by Dr Douglas Hanahan, a cancer scientist at the Swiss Institute for Experimental Cancer Research in Lausanne, showed that cells from deadly forms of aggressive breast cancer — that are equally difficult to treat — express genes associated with neuron signalling (3).
The studies highlight just how resilient cancer cells are and how they can adapt, even in an apparently unwelcoming environment like the brain. Although it’s not all bad news. Gaining a better understanding of how tumour cells survive and flourish could help researchers develop novel ways to combat these difficult-to-treat cancers. For example, cutting off the connection between tumour cells and neurons to halt cancer growth.
In their studies, Winkler and Monje demonstrate that an epilepsy drug can slow the progression of glioma in mice. The approach has not been tested in humans just yet. The biggest challenge will be showing that any treatment used to break synaptic connections between tumour cells and brain cells does not also harm crucial connections between neurons. This may prove difficult to achieve.
(1) Venkatesh, H.S. et al. Electrical and synaptic integration of glioma into neural circuits. Nature (2019). DOI: 10.1038/s41586-019-1563-y
(2) Venkataramani, V. et al. Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature (2019). DOI: 10.1038/s41586-019-1564-x
(3) Zeng, Q. et al. Synaptic proximity enables NMDAR signalling to promote brain metastasis. Nature (2019). DOI: 10.1038/s41586-019-1576-6