Brain tumours’ shared metabolic tricks hint at new approach to treatment

When we hear the word ‘metabolism’, food is likely to be the first thing that springs to mind. But there’s much more to metabolism than getting energy from what we eat.

Metabolism spans all of the biochemical reactions happening in our bodies right now. It covers the energy we generate by breaking down big molecules from our diet, but also how we use that energy to make everything our cells need to keep ticking over.

This means that metabolism can act as a barometer for cellular health. And a cell turning cancerous can shift these signals in tell-tale ways.

Studying the characteristics of a tumour’s metabolism is being used to improve diagnosis, and help monitor if a drug is working or not sooner than we can today. But now scientists think that it could be revealing something else, at least for brain tumours.

By listening to the chemical chatter of several different types of brain tumours, new research, published in the journal PLOS ONE, has found that, unexpectedly, these tumours share distinct patterns of metabolism. And this was even true for tumours that didn’t start in the brain, but spread there from another part of the body.

This suggests that tumours in the brain are co-opting certain cellular controls in similar ways to thrive in this unique environment, the authors say. If confirmed, the work potentially opens up new avenues for treatment research.

Sweet connections

The Cancer Research UK-funded team became interested in the metabolism of tumours because cancer cells display a characteristic metabolic quirk. Unlike healthy cells, cancer cells generate fuel by breaking down sugar – in the form of glucose – using a process that doesn’t require oxygen, even when the cells have plenty of oxygen available. This is called the Warburg effect.

In this latest study, the scientists were looking for particular patterns in the metabolism of brain tumour cells. More specifically they were looking for relationships, or correlations, in the levels of molecules produced during metabolism, known as ‘metabolites’.

“Inside the cell, these metabolites have a complex network,” says lead researcher Dr Madhu Basetti, from the Cancer Research UK Cambridge Institute.

“We examined the metabolic content of all cells from a tumour, looking for connections.”

The team used available data on the chemical contents of 378 patient samples from 5 different types of brain tumour: glioblastomas, astrocytomas, meningiomas, oligodendrogliomas, and tumours that had spread to the brain, called brain metastases.

Plenty in common

To their surprise, the researchers found that these tumours all had strikingly similar metabolism.

“The results were a big shock; all of the tumour types had virtually the same pattern of metabolite relationships,” said lead researcher Professor John Griffiths, also from our Cambridge Institute.

The results were a big shock

– Professor John Griffiths

“And these relationships weren’t just between the single chemicals that we expected to interact with one another; we observed correlations between whole pools of similar chemicals. This novel result suggests that cells have mechanisms to control the size of these pools, rather than just the amount of each individual chemical.”

These findings were particularly unexpected because they were so similar in tumours that originated from many different types of cell. Meningiomas for example arise from the protective tissue that encases the brain and spinal cord, while astrocytomas originate in the cells that support and feed nerve cells.

But what was even more perplexing for the scientists was the finding that the brain metastases also seemed to share these patterns in their metabolism, even though they began in completely different parts of the body. The tumours that they had spread from included lung, breast, oesophageal and kidney cancers.

Breaking up relationships

The brain is a highly specialised environment, so the researchers think that the tumours could be adopting similar survival strategies in order to grow in this unique area of the body.

“Perhaps there are a set of tricks that brain cells use to communicate with one another and feed each other, and when cancer cells live in the brain, they have to use these same tricks themselves,” Griffiths says.

In the future, it might mean that we could develop drugs that specifically damage these survival mechanisms

– Professor John Griffiths

If further research backs up this idea and identifies these tactics that brain tumours need to grow, then that could have implications for treatment research.

“In the future, it might mean that we could develop drugs that specifically damage these survival mechanisms,” says Griffiths.

While that possibility is a long way off, this finding will hopefully fuel further research into this fascinating area. And the more knowledge that scientists develop, the more likely they are to find new ways to tackle the disease. With brain tumour survival remaining stubbornly low, that’s something we urgently need.

Justine