Fascin-ating insights into how pancreatic cancer spreads

Today around half of people diagnosed with cancer will survive for at least 10 years. And survival rates in the UK have doubled over the last 40 years.

But there are certain cancers that refuse to follow this trend. Pancreatic cancer is one of them.

The early signs and symptoms can be hard to spot, and the disease is often diagnosed at a later stage when it is much harder to treat.

This means that less than three per cent of patients survive for 10 years or more.

That’s why – along with other harder-to-treat cancers – we’re sharpening our focus on pancreatic cancer and picking up the pace of research into this devastating disease.

Promising research from our scientists in Cambridge is already showing how the immune system could be harnessed to target pancreatic cancer.

And today, a team of our scientists from the Beatson Institute in Glasgow – led by Professor Laura Machesky – publish their latest research in the journal Gastroenterology. Their findings show how an important protein that helps cells move, known as fascin, could contribute to how pancreatic cancer spreads.

Bundles of protein

Like this elastic band, fascin bundles actin fibres together

The fascin protein has been on Professor Machesky’s radar for some time. It corrals another key molecule in cells called actin, which forms long fibres inside our cells. Fascin bundles actin fibres together to form part of a cell’s internal skeleton.

The dynamic ways in which this skeleton is repeatedly built, and then dismantled, play a vital role in controlling how cells move. Cells that move around a lot – like some nerve cells – make a lot of fascin. And some developing cells in an embryo also produce more of the protein.

But certain groups of normal adult cells – the type you’d find lining your digestive system, body organs or abdomen – don’t make much fascin, so the cells tend not to be very mobile.

How’s this linked to cancer? Research has shown that fascin can be produced in vast excess in some cancers – including breast and bowel cancer cells – and this has been linked to poorer survival from these types of cancer.

This has sparked a lot of interest in fascin, especially in how it may control the way cancer cells move and spread to other parts of the body – a process known as metastasis – which is intimately linked to the deadly later stages of cancer.

The highs…

Pancreatic cancer cells with lots of fascin (green) – image provided by the researchers

In the latest study the team scoured samples of human and mouse tumours, looking for which tumours contained excess fascin.

Here they landed on pancreatic cancer.

“Of all the different tumour types we looked at in mice, the pancreatic tumours had the highest levels of fascin – but the normal pancreas cells had none – it was really striking,” Professor Machesky told us.

They then looked at samples from 122 pancreatic cancer patients and saw the same pattern as in the mice – fascin was produced at much higher levels in the tumour cells than in the normal cells.

And like with other types of cancer, the higher the levels of fascin, the poorer the survival rates.

But why?

…and lows of fascin

Turning their attention back to the mice that develop pancreatic cancer, the team bred a different group of mice that were still prone to developing the disease, but their cells were engineered to no longer produce fascin.

These mice developed fewer tumours, and the tumours that did grow were smaller than normal.

“This came as a bit of surprise to us,” Professor Machesky said, “it means that fascin might have a role to play in how these tumours develop, not just in how the tumour cells move and spread, which would’ve been our first predication,” she added.

But that first prediction was also correct – when the team looked at how successful the tumour cells were in spreading to areas close to the pancreas they found that, in the mice that couldn’t produce fascin, the cells were far less able to spread.

Spikes, ruffles and pushy cells

Looking at their research first hand – like in the video below – you can see that failing to make fascin puts a halt on how spritely these pancreatic cancer cells are.

• Watch a video of the team’s latest findings

Fascin is helping these cells make the fast-moving spikes and ‘ruffles’ in their membrane that help each cell explore the world around it.

When pushing through into the alien environment beyond the tumour, these spikes and ruffles seem to be really important as the cells set up a new home that could become a secondary tumour.

The next challenge is how to stop them.

What next?

Professor Machesky and her team are looking at ways of stopping fascin working inside cells, as well as piecing together the finer molecular details of how fascin helps pancreatic cancer cells move more easily.

“We’re working with Dr Martin Drysdale and his team at the Beatson on some interesting ways to stop fascin working,” Professor Machesky told us.

“It’s the sort of collaboration that would be difficult outside the institute environment we work in,” she added.

“It’s really exciting, a drug company might see the early stages of developing drugs against fascin as a risky bet, but we can work with other labs on these early stages, building up the data needed to turn this in to something that could benefit patients in the future.”

It’s still early days though, and more research will be needed to find the best way to put the brakes on these cells.

Research like this shows how our scientists are chipping away at the pancreatic cancer puzzle, and making new discoveries that could help increase survival rates for patients in the future.

Nick

Reference

• Li A, et al. (2014). Fascin Is Regulated by Slug, Promotes Progression of Pancreatic Cancer in Mice, and Is Associated With Patient Outcomes, Gastroenterology, 146 (5) 1386-1396.e17. DOI: 10.1053/j.gastro.2014.01.046

Image credit: Asparagus image from Wikimedia Commons