Most people think cancer becomes deadly when a tumor grows too large. But that’s not exactly true. In many cases, the real threat comes when cancer spreads.
This process, called metastasis, is responsible for the vast majority of cancer deaths. It’s not the tumor in one spot; it’s the new ones appearing in the brain, bones, or lungs that cause the damage.
Now, researchers have found something surprising: it might not be the cancer cells themselves that decide to spread. It could be the journey they take through the body. Being squeezed through the body’s tiniest blood vessels may transform them into a more dangerous version of themselves.
Testing cancer cells in tight spaces
Our blood vessels get incredibly narrow, especially in the capillaries – tiny tubes just wide enough for blood cells to pass through. Experts built a special lab device that mimics how these vessels work.
The researchers wanted to see what happens when cancer cells are forced through narrow spaces, like what they’d experience moving through blood.
The team used melanoma cells for the experiment. These are skin cancer cells known for spreading quickly and aggressively.
The device was made from a soft plastic material and contained channels as small as five micrometers wide – far narrower than a human hair. When the melanoma cells were forced through these channels, something changed.
Cells reprogrammed under stress
Study lead author Dr. Giulia Silvani created the device at the Australian National Fabrication Facility, a joint venture between UNSW, the University of Sydney, and UTS.
“Within 15 minutes of being squeezed through the smallest channels, we observed how the melanoma cells became physically deformed,” said Dr. Silvani.
“When we analyzed the cells, we detected proteins linked to cancer spread and stem cell-like behavior – suggesting that the mechanical stress had reprogrammed them to adopt this new state.”
That’s important. Cancer cells that act like stem cells can multiply more easily and survive in different environments. This makes them much more likely to form new tumors in other parts of the body.
Squeezed cells grow more tumors
To test whether these changes made a difference in a living system, the researchers injected the “squeezed” melanoma cells into mice with weakened immune systems. These mice were also given unsqueezed cancer cells for comparison.
After 30 days, the results were clear. Mice injected with the squeezed cells developed far more tumors in the lungs, bones, and brain. The squeezing made the cells more aggressive and more likely to spread.
“One of the most exciting aspects of this project was the chance to study metastatic cancer cells in a way that hasn’t been possible before,” said Dr. Silvani. “Their journey through the body is so hidden, leaving little trace and making them incredibly difficult to capture in action.”
“We were able to recreate that journey in the lab, giving us a rare glimpse into the moment when these cells switch into their most aggressive state.”
Pressure reshapes cancer cells
This new discovery supports a longstanding idea among scientists: that mechanical pressure – like being squeezed through narrow blood vessels – can change cancer cells. But now, there’s real evidence to show how it happens.
Professor Kris Kilian, who co-authored the study, explained what this could mean going forward.
“These results open up new possibilities for prognosis and treatment, by targeting the mechanical forces that lead to metastasis,” he said.
New paths for diagnosis and care
One future approach could be using imaging, like MRI scans, to find areas in the body with lots of tiny blood vessels.
These spots might be more likely to trigger the kind of cellular change seen in the study. Doctors could then watch those areas closely or even find ways to reduce the risk of cells squeezing through.
Another possibility is to look at cancer cells floating in a patient’s blood. Doctors could then test how easily those cells can transform under pressure. This could help doctors figure out how likely the cancer is to spread in a specific person.
“The point is, it used to be thought that it was just this extremely rare type of cell that found its way from a primary tumor to a spot where they could invade,” said Kilian.
“But no, in some cases it’s actually the squeezing that changes the cell into this rare type, and it could put cancer researchers in a much stronger position to devise new treatment strategies.”
Breast cancer shows blood effect
About 90 percent of the work so far has focused on melanoma. But Kilian believes this squeezing effect might show up in other cancers too. He mentioned early results in breast cancer experiments look promising. More testing is planned across different types of tumors.
“I believe we’ll find evidence that many solid tumors metastasize this way – we’re already seeing compelling evidence when we repeat these experiments with breast cancer – and I’m looking forward to testing a range of cancer cell types in the lab,” he said.
Dr. Silvani is also eager to continue the work. She sees huge value in using engineering tools to better understand how cancer behaves.
“Watching this idea grow from a spark of intuition into a real discovery has been deeply inspiring,” she said. “It’s a powerful reminder of what can be achieved when engineering and biology come together.”
“Cells are intricate machines, and unraveling their mysteries requires precise design and innovative tools, guided by the insights biology provides.”
This discovery doesn’t promise a cure. But it’s a fresh way of thinking about how cancer spreads – and a step closer to finding new ways to stop it.
The full study was published in the journal Nature Communications.
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