Do These World-First Images Hold Key To Cancer?

A breakthrough in imaging techniques could enable scientists to watch the moment that cancer first strikes, holding out the prospect of radical new treatments. In a world first, researchers at Dundee University managed to film healthy, live cells within an embryo dividing and redividing after developing a new way of using a powerful microscope.

{mosimage}The film shows the birth of neurons – which form the brain and nervous system – as cells in a chicken’s egg divide into two, a nerve cell and a “mother cell” that goes on to divide again. This is the first time this stem cell pattern of division has been witnessed in real time. Stem cells can form any kind of cell in the body and it is thought that cancers may occur when those in body tissue make some kind of “mistake”.

The team now plans to artificially induce a cell to become cancerous so they can watch what happens inside when a cancer is born.

This process is poorly understood at present and actually seeing what occurs could lead to a way of preventing it. In almost all cancers, stopping them from spreading renders them relatively harmless.

Cancer specialists described the film as excellent work. One expert expressed the hope that a film of a healthy cell turning into a cancerous one could shed light on the “critical thing” – the trigger for the disease in a cell.

One of the lead researchers, Dr Jason Swedlow, of Dundee University’s College of Life Sciences, said watching the film of nerve cell division for the first time was a “eureka moment”.

“We called the first really good film, Totally Rocking Movie’. It’s one of those amazing moments – you get those once every ten years or so. It’s an amazing thing to be able to watch this process,” he said.

Dr Swedlow, along with colleagues Dr Kate Storey and Arwen Wilcock, who published a paper in the journal Development this month, is now looking to use genetic techniques to “perturb” a cell so it becomes cancerous and try to film what happens.

“If we can learn a little bit about when things go wrong and what makes them go wrong – if you have a model of how these events happen – then you have some ability to start understanding how it happens in the first place and what to do to prevent it happening,” he said.

“That would be an important contribution.”

Scientists have been able to see ordinary cancer cells dividing, but only a long way into the disease’s formation. The Dundee researchers hope to film the point the disease begins.

“What we really want to do is be there at the first event. That’s much, much harder. Can we actually watch that initial event? Good question,” Dr Swedlow said.

“Gosh, I hope so. That is exactly the question, but I think it’s a little premature and optimistic to say we’ll be able to watch that.

“What we are starting to do now is the perturbations that lead down those lines. What does that look like and what do the cells do? What happens when you make a mistake in cell division?

“Stem cells have this ability to divide over and over again and produce cells that can differentiate.

“When you are dividing, life is risky. It’s a scary time when mistakes can happen. There’s a lot of interest in how those mistakes occur and ultimately lead to disease.”

However, he warned that seeing what happened to chromosomes and other components within a cell might not lead to a sudden breakthrough, like a drug that could “fix” mistakes in cell division.

Dr Storey said the film had revealed that even the angle at which cells split can have a fundamental impact on their future life.

“Cells divide in this way to generate new nerve cells. It is how the nervous system is built up,” said Dr Storey, a developmental biologist.

“It is important that some cells keep dividing in order to make a large and complex nervous system with a variety of cell types.

“Understanding what directs this kind of stem cell division in the nervous system informs our ability to control such cells which could in the future offer the potential for us to repair or replace damaged cells.”

Professor Karol Sikora, a special adviser to the World Health Organisation and an internationally respected cancer doctor, said he would be eager to see the film of a cell becoming cancerous.

Speaking of the Dundee study, he said: “It sounds very interesting. It’s a very good approach. People have tried to do this before and not really got much out of it because they haven’t had the technology.”

Professor Sikora said there was a gap in knowledge about cancer that a film of the cell might fill.

“We don’t know the critical thing. One day a cell is normal. It may have accumulated a certain amount of genetic damage but it’s still normal,” he said.

“The next moment, it’s cancerous. What’s actually the trigger for it? If we understand that, it may be possible to use that discovery to develop drugs.”

Dr Mark Matfield, scientific consultant for the Association for International Cancer Research, which is based in St Andrews, said: “This is excellent work. This technique will open up new lines of research that should tell us a lot more about how the brain develops and may help work out ways to repair damage to the brain or spine.

“The idea of applying this to study how cells become cancerous is interesting and may also yield new insights.”
Focus on nervous system diseases

Filming the moment a nerve cell is born could help to treat a whole range of diseases which affect the nervous system.

In microcephaly, which means “small head”, people have a normal brain and body structure, but these are smaller than usual because there are fewer cells.

This could be because when cells divide, too many of them become two “daughter” cells and not enough “mother” cells – which can carry on dividing – are produced during early development of the child.

Highlighting the process of cell division has led to insights into the role of symmetry and angles of cells as they divide in determining which produce two daughter cells and which result in one daughter and one mother cell.

Being able to influence the production of these different types of cells could potentially lead to a way of treating microcephaly, although scientists warn that interfering with cell division would be a major step.

The new film should also help basic research on the nervous system.

Ultimately, it could lead to new treatments for a whole range of diseases affecting the brain and nervous system, including motor neurone disease, and spinal cord injuries.

However, Dr Kate Storey, one of the Dundee University research team, cautioned that what they had achieved so far was a greater idea of how the nervous system is created and that any new treatments would likely take a considerable time to develop.

She said: “That’s a long way down the line. We need to be realistic about it. We are really looking at the basic building blocks of the nervous system and how it works.”

Q & A: WHAT NOW?
Why is this a scientific breakthrough?

For the first time, researchers were able to film nerve cells being “born” in real time and within their natural environment in a chicken egg.

The film shows a cell dividing into two in a manner similar to the way that stem cells, which can turn into any kind of body tissue, do so.

Crucially, the success of the film will enable scientists to watch the way the process actually happens in the body – rather than in a test tube or other alien environment – over a period of time.
What is the next step?

The researchers at Dundee University have already begun work to try to image the birth of a cancer cell, the actual moment when a healthy cell becomes cancerous.

It is thought that many cancers are the result of a stem cell which makes a mistake when it divides.
What would this mean for cancer research?

While it is known that damage to cells – from smoking or sunlight for example – can lead to cancer, what actually gives rise to the “birth” of the first cancerous cell is not well understood.

To be able to see what physically happens to a cell and its inner components might shed new light on the disease, leading to new treatments.
Apart from cancer, what else might the film be used for?

It shows the basic, stem-cell-like process that leads to the creation of the brain and nervous system.

A greater understanding of the fundamental way that this happens could lead to new ways of repairing any kind of damage to the nervous system or replacing lost tissue in the future.

Already, the researchers have found that the angle of the cell influences whether a nerve cell divides into two “daughter” cells – both become nerve cells – or one daughter and a “mother” cell that can continue dividing.

Stem cells are seen as future sources of major medical breakthroughs, as they appear to hold out the prospect of regenerating human tissue, regrowing areas that have been damaged by disease or injury.

In the animal world, flatworms, or planaria, have remarkable powers of regeneration, even including the ability to regrow a head, while some lizards can shed their tail to help them to escape predators and then they simply grow a new one.
How was the breakthrough made?

A combination of expertise in different aspects of microscopy, cell biology and computing at Dundee University enabled the film to be made using existing technologies.

HOW CELLS DIVIDE

1. The process of mitosis, in which cells duplicate their chromosomes (the part of the cell that carries the genetic code), gets under way.

2. At 14 minutes before the start of the split, a ‘cleavage’ develops in the cell, shown by the pink line across it.

3. At zero hour, the dotted red line shows the emerging new cell. The birth of the ‘daughter’ cell has begun in earnest.

4. The ‘daughter’ is still joined to what will go on to become a new ‘mother’ cell (in green), which will be able to divide again. But gradually the cells begin to separate.

5. At 17 hours 19 minutes after zero hour, two distinct new cells are seen for the first time.

6. The ‘daughter’, seen at the top, is now clearly a separate cell from the ‘mother’ or progenitor cell at the bottom.