A new biomaterial developed by researchers from The University of Western Australia is providing fresh insights into the way cancer cells escape from tumours and spread through the body.
Metastasis – the development of malignant growths distant from the original cancer site – is the leading cause of cancer-related deaths in humans worldwide but scientists do not yet fully understand how it occurs.
Led by Associate Professor Yu Suk Choi and Dr Danielle Vahala from UWA’s School of Human Sciences, researchers have developed a three-dimensional microgel that is making it easier to study the physical environment surrounding cancer cells and how that environment influences their ability to migrate.
“Cancer cells do not exist in isolation,” Associate Professor Choi said. “They are surrounded by tissues that can change as a tumour grows, becoming stiffer and developing tiny spaces and pathways between fibres that cancer cells can then use to move through the body.”
Dr Vahala said traditionally it had been challenging to study this migration in the laboratory.
“This is because the changing stiffness of a material can also change the size of the spaces between cells,” she said.
The team has developed a 3D tissue model that mimics the physical structure of tumours more closely than existing laboratory systems.
Using the new model, they were able to track how breast and pancreatic cancer cells behaved in environments with different levels of stiffness and space.
They found aggressive cancer cells were particularly sensitive to these physical conditions and were able to move more readily through the imitation tissue.
“Surprisingly, we also found that less aggressive cancer cells can become mobile when they detach from neighbouring cells and enter small spaces in the surrounding tissue,” Associate Professor Choi said. “This movement increased when the environment was stiffer.”
He said the results suggested that even cancer cells not normally considered invasive had the potential to migrate under the right conditions.
“Understanding these conditions gives us important clues about how metastasis begins and how we might be able to stop it.”
Dr Vahala said the findings reinforced that genetic changes or chemical signals were not the only factors that influenced cancer cells.
“This research confirms the physical environment around a tumour also plays a major role in whether cells remain in place or start moving,” she said.
The team believes the findings could pave the way for better treatments aimed at preventing cancer spread and reduce the gap between laboratory studies and what happens inside real tumours.
“Our model could also have applications beyond cancer research, including studies of tissue repair, wound healing and other diseases where cells move through complex environments,” Associate Professor Choi said.
Published in Advanced Science, the research was a collaboration between UWA researchers from the School of Human Sciences, School of Engineering, UWA Medical School, BRITElab led by Professor Brendan Kennedy at the Harry Perkins Institute of Medical Research, and researchers from the University of Sydney, Yonsei University (Republic of Korea) and Soonchunhyang University (Republic of Korea).
Image at top: 3D render of space jam-med granular hydrogel mimicking tumour microenvironment. Credit: Dr Danielle Vahala
