Brain cancer hijacks neuroplasticity to grow

A topic I’m super interested in right now is the similarities between how our bodies regenerate and how cancers spread. The fact that cancers and healing share common mechanisms/factors is pretty intuitive: both processes involve cells forming new connections and growing.

Today we’ll go through a new paper detailing how cancer hijacks features of neuroplasticity to spread more aggressively.

The Question

Gliomas are are the most common brain cancer, and one of the most lethal. Like most cancers, gliomas rely on interactions with other non-cancerous cell types to grow and spread. Specifically, gliomas interact with healthy neurons to regulate their behavior and even their formation.

Given the aggressive growth of gliomas, this weeks authors asked if glioma progression could take advantage of a well known neuronal growth signal - the protein BDNF.

BDNF, or brain derived neutrophic factor, is a protein that regulates neuronal plasticity, memory, and learning in healthy brains. The authors previous work showed that BDNF increased glioma cell growth.

The Answer

To test if BDNF was important for glioma progression, the authors tracked the survival of mice with gliomas. In mice with that don’t express the BDNF protein or its receptor, the survival rates were significantly higher than in mice that have them. The graphs below show this trend.

Right off the bat this told the researchers that sensing BDNF is important for glioma progression. Without it, the cancer wasn’t able to spread as effectively and became less lethal. This is convincing evidence that the cancer hijacked a typical method of brain plasticity to help itself grow. The next question was: how? How does sensing BDNF actually lead to cancer growth?

The main way seems to be through increasing cancer proliferation, with proliferation being the processes of cells dividing to make more cells.

Interestingly, when BDNF was given to glioma cells by themselves, the fraction of cells proliferating went from ~20% to 30%, or roughly a 50% increase. However, when they did the same thing but cultured the glioma cells with neurons, the fraction went from 20% to 60%, about a 300% increase.

This difference suggests that BDNFs role in glioma progression is probably more complicated than just “it makes the cells grow more”. There’s some sort of synergistic effect between the presence of neurons and BDNF.

Next, the authors tried to tease out how BDNF contributes to gliomas. Given the neuron proliferation data discussed above, one possible explanation was that it increases the strength of the neuron-to-glioma connection.

This connection can be measured by the strength of the electrical signal the cells send. The graph above is showing this signal over time. On the left, the larger peak signal tells us that the cells given BDNF (blue line) send stronger signals than the cells without BDNF (grey). When the BDNF sensor on the cells is removed (right graph), the signals become the same.

This shows that BDNF works, at least partially, through increasing the strength of the neuron-to-glioma connection.

There’s a lot more biology in the paper if you’re interested, but I’m going to leave it here for today.

Overall, the authors found that BDNF helped gliomas proliferate, particularly in the presence of neurons. They also found removing or blocking BDNF signaling improved survival time, potentially identifying BDNF as another target for glioma cancer therapies.

This is just one of many examples of cancer hijacking our bodies response system to help itself grow. In normal conditions, BDNF helps our brains and other neural tissues heal and grow stronger. In gliomas, this process is taken advantage of to do the same for cancers.

See you next week for more science,

Neil

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