Tracking down brain tumour stem cells

Dr Steven Pollard and his team have found a way to grow brain tumour stem cells in the lab

Previously, we highlighted Cancer Research UK’s role in brain tumour research. In this post we’ll take a look at a fascinating piece of recent research in this area that we helped support.

There are many different types of brain tumour, but the most common – and also the most aggressive – is malignant glioma. Gliomas are complex cancers, and tumours can vary widely between patients, making the disease difficult to accurately grade and treat.

Some researchers think that this complexity may be due to the presence of cancer stem cells. And now Cancer Research UK-funded scientist Dr Steven Pollard and his team have developed a way to grow glioma stem cells in the lab, providing an important new resource for studying this disease and developing new treatments.

The team published the results of their work in the journal Cell Stem Cell.

In recent years, a number of research teams have been trying to grow colonies of brain tumour cells (known as cell lines) in the lab, but these attempts have been hampered by significant technical problems. As a result, it’s proved difficult to track down and isolate brain tumour stem cells in these lab systems, and to find out what makes them tick.

Over recent years, Dr Pollard and his colleagues have managed to develop techniques for growing healthy brain stem cells in the lab. In their latest research, they take this one step further, and reveal how to capture glioma stem cells in the same way.

First catch your stem cells…

To develop their glioma stem cell lines, the researchers started with samples from surgically removed tumours.  They broke up these tumour samples to separate the cells, mixed them with nutrient broth to help them grow, and put them in plastic dishes coated with a molecule called laminin.

Laminin is found in the brain, and helps healthy stem cells to grow. So the researchers figured that it would probably help cancer stem cells to grow too.

As you might expect from such a mixed starting material, many different types of cells began growing in the dishes. But after a week or so, lots of them died, leaving only the ‘immortal’ stem cells responsible for fuelling the original tumour.

Using this technique, the team managed to create cancer stem cell lines from three different types of brain tumour – three cases of glioblastoma multiforme, one giant cell glioblastoma, and one oligoastrocytoma. And so far, they have grown these cell lines in the lab for more than a year.

What can we do with them?

Dr Pollard and his team have investigated their new cancer stem cell lines in depth, assessing the molecules found within them, and looking for genetic abnormalities linked to the cancer.

The team also tested the characteristics of the stem cells, to see how they behaved as conditions changed..  They found that the cells behaved just like cancer cells would be expected to, forming new tumours and producing different types of cells.

Finally they made a really exciting discovery.  They used these new cell lines to test potential new drugs to see if they could stop them growing or even kill them.  In a ‘proof-of-concept’ experiment, the researchers tested three of their cell lines with 450 different cancer drugs that are currently in clinical use. The team added doses of the drugs to samples of the cells, and watched the effects down a microscope. They also tested a ‘control’ line of non-cancerous cells.

The team found that 38 drugs had some effect on at least one cell line, including a number of drugs that affect neurotransmitters (chemicals that send signals within the brain) – particularly the serotonin pathway.  The also discovered that the neurotransmitter-disrupting drugs didn’t have an effect on the control cells, suggesting they were only active against brain tumour stem cells – an important characteristic for a potential brain tumour drug.

Where next?

This painstaking research opens two doors for further exploration, which will hopefully take us closer to developing new treatments for brain tumours.

Firstly, the technique that Dr Pollard and his team have developed for growing brain tumour stem cells will allow researchers around the world to create more cell lines, helping us to understand more about the genes and molecules involved in brain tumours.

This sort of ‘methodology’ discovery – where scientists describe a new technique to study the world around us – can be every bit as vital as research that reveals potential new treatments. Researchers can now use this new tool in their toolbox to study how these cells behave in tumours and make further discoveries.

But as well as this, Dr Pollard’s team’s work suggests that looking for drugs that affect the serotonin pathway could lead to new ways to treat glioblastoma, although more research needs to be done to back this up.

Although these cell lines aren’t an instant solution to many of the challenges of researching brain tumours, they are an important resource for scientists around the world who are working to beat this disease.  And we hope to report on much more progress in the future.

Kat

Reference:

Pollard, S., et al (2009). Glioma Stem Cell Lines Expanded in Adherent Culture Have Tumor-Specific Phenotypes and Are Suitable for Chemical and Genetic Screens Cell Stem Cell, 4 (6), 568-580 DOI: 10.1016/j.stem.2009.03.014