Science Surgery: ‘How do tumours ‘know’ where to spread?’

Our Science Surgery series answers your cancer science questions.

James asked: “How do tumours ‘know’ where to spread?”

“It’s hard to talk about tumours ‘knowing’ something,” says Professor Laura Machesky, an expert in how cancers spread at the Cancer Research UK Beatson Institute in Glasgow. “But it does seem like they know what they’re doing sometimes.”

This, Machesky says, is because cancers have “predictable patterns”, meaning certain cancers usually spread to particular parts of the body.

Breast cancer, for example, usually goes to places like the lungs, liver brain or bones if it spreads, whereas pancreatic cancer is more likely to spread to the liver.

“It makes it look like the cancer knows what it’s doing,” says Machesky. “But really we think that cancer cells are being randomly shed from the tumour – the cells come off and they get distributed around the body – and the majority of them die.”

A few of these free-wheeling tumour cells survive our bloodstream, finding a place to settle in another part of the body, if the conditions are right.

What do cancer cells need to spread?

When cancer cells break away from the tumour, they face a tough environment. There’s a good chance that they’ll be broken up by the flowing force of our bloodstream, like a raging river tossing a boat around.

But if the cells do survive this journey, they then need to land in welcoming place where there are nutrients, oxygen – and in a place where they’re protected from the immune system.

If they find all of these things, they may be able to survive in their new home in the body and form a secondary tumour.

“I like to think that, for example, if a million cells get out of a tumour and spread all around the body randomly then only a few of them will survive,” says Machesky.

This is often called the ‘seed and soil’ theory of cancer spread. The theory goes that cancer cells are like seeds being dotted around the body, but to grow and become a secondary tumour they need to find fertile soil to settle in.

And it seems that pancreatic cancer cells are somehow better able to settle and survive in the liver than in other places. But why?

Scientists think this could be down to sticky hooks found on the surface of cancer cells. These hooks act a bit like Velcro, allowing cells to latch on and stick in certain places in the body. Normal cells have these hooks too, allowing them to survive and form larger structures like organs where specific cell types stick together in an organised way.

And if different types of cancers have different hooks on their surface, they may find it easier to stick in different places.

But it might not be quite that simple. Scientists are beginning to discover that far from a game of chance, tumours might actually be able to alter tissues in other parts of the body, stacking the odds of survival in their favour.

Prepping the soil

“Tumours can cause changes around the body, not only at the site where they’re at,” says Machesky.

Take the example of a pancreatic tumour: “If you a tumour in your pancreas then there may be changes happening in the liver that make it easier for the tumour to spread there.”

One of the things that may help to prep the soil for tumour spread are tiny bubble-like structures called vesicles, which we’ve blogged about before. These microscopic blobs can break off from cancer cells and float around the body, carrying messages on their surface.

Machesky says these vesicles could help to prepare certain parts of the body for tumour spread. For example, the vesicles could signal to the liver to become a bit inflamed. This might cause the liver to have leaky blood vessels, allowing more oxygen into the tissue. And it’s the culmination of these changes that may help to create an environment that’s easier for spreading tumour cells to settle and grow in.

Stopping spread

Scientists have learnt a lot about how tumours spread. But Machesky thinks there’s still more to come. And a big problem with studying cancer spread is finding a way to recreate it in the lab.

“When we’re studying cancer spread, we’re talking about a few cells initially escaping from the primary site and sitting quietly in another place in the body and there isn’t a good model for this,” she says. “There isn’t a really clear way to see how to study it, so I think that’s one of the challenges.”

But while the problem isn’t simple, the benefits of understanding cancer spread could be big. Machesky says there’s a lot of excitement about developing ‘anti-spread’ treatments that target tumours’ likely second homes before the cancer has a chance to move. By making the sites unfavourable for tumours to survive, they may be able to stop the spread before it’s even started.

“That’s kind of hard to do because you don’t want to take someone with breast cancer whose successfully been treated and give them medicine that goes into their brain without thinking really carefully about the risk,” says Machesky.

Stopping cancer spread might be tricky, but it’s something that scientists are becoming increasingly interested in.

“In the early days we focused most of our efforts on the primary tumour,” says Machesky. “But now, we’re starting to think about how to target those sites where tumour cells might be hiding out.”

Katie

We’d like to thank James for asking this question. If you’d like to ask us something, post a comment below or email [email protected] with your question and first name.