Healthcare (Commonwealth Union) – In Australia, nine out of the ten leading causes of cancer-related deaths are solid tumours. In most cases, however, it is not the primary tumour itself but the cancer’s spread to other parts of the body—known as metastasis—that proves deadly.
Researchers at the University of New South Wales (UNSW) have now identified a potential factor that may trigger metastasis: the compression of cancer cells by tiny blood vessels, which transforms them into a different cell type capable of forming new tumours.
In a study that appeared recently in Nature Communications, the team described the way they engineered a biomedical device that mimics blood flow via the narrowest vessels of the body. They found that when human melanoma cells are pushed through channels smaller than 10 micrometres—roughly one-fifth the width of a human hair—the cells start to act more like stem cells, acquiring characteristics that could help them survive, migrate, and initiate new tumours.
This discovery supports a long-standing hypothesis in cancer research: that the mechanical stress of squeezing through narrow blood vessels may make cancer cells more aggressive. While these results were observed in lab-based devices and in mice, they provide a fresh perspective that could guide future studies and strategies aimed at halting cancer spread.
Co-author Professor Kris Kilian from the UNSW School of Materials Science and Engineering and School of Chemistry stated that for years, the mechanisms behind how cancer reaches distant organs have remained unclear.
He indicated that while most tumor cells traveling through the bloodstream are poorly equipped to survive and establish themselves in other organs, some patients still experience high rates of metastasis.
Professor Kilian further pointed out that their research offers a fresh perspective, showing that cancer cells can be prompted to become more capable of forming new tumors. He indicated that this suggests that such changes may occur before metastases develop in areas like the bone and brain.
The researchers developed a device smaller than a postage stamp that replicated how blood moves through the human body, using progressively narrower channels to simulate the tiny capillaries found in various tissues.
Dr Giulia Silvani, the study’s lead author, designed the ‘microfluidic’ device on site at the Australian National Fabrication Facility (ANFF), a nanotechnology collaboration between UNSW, the University of Sydney, and UTS. She constructed the channels from PDMS, a biocompatible, flexible plastic, with widths ranging from 30 micrometres down to just 5.
Dr Silvani then flowed a nutrient-rich solution—similar to blood plasma and containing human melanoma cells—through the device at a rate comparable to blood movement in capillaries.
She stated that after only 15 minutes of passing through the narrowest channels, they were able to see the melanoma cells becoming physically deformed.
“When we analysed the cells, we detected proteins linked to cancer spread and stem cell-like behaviour — suggesting that the mechanical stress had reprogrammed them to adopt this new state.”
To determine if these compressed cancer cells had a greater tendency to spread throughout the body, the team injected them into mice with compromised immune systems, which allowed the human melanoma cells to survive and grow. After 30 days, the mice that received the compressed cells showed a markedly higher number of tumours in the lungs, bones, and brain compared with mice injected with uncompressed melanoma cells. The researchers suggest that this indicates the compression makes the cancer cells more aggressive and capable of forming new tumours.
Dr Silvani pointed out that one of the most thrilling parts of this study was the opportunity to investigate metastatic cancer cells in a way that has not been possible on prior conditions.
