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The chip, a small plate where cancer cells, nerves and blood vessels grow, was developed by researchers at Linköping University, Sweden, in collaboration with colleagues at the Polytechnic University of Milan in Italy.
In the body, solid tumours grow in close interaction with blood vessels, nerves and the surrounding tissue. The new chip, which replicates basic organ functions, provides a model of head and neck cancer to demonstrate that interaction and show that the concept works, all on a system roughly the size of a postage stamp.
“Rather than having to carry out research on animals or test potential drugs in humans, we want to be able to carry out tests in a single microsystem in the laboratory. If we want to understand why a tumour grows, spreads, causes pain or resists treatment, we need models that can replicate the interactions between the tumour and its surroundings,” said Pierfrancesco Pagella, senior associate professor at Linköping, who led the study.
To replicate interactions in the body, the researchers developed the model in three steps. First, they developed a material designed to mimic the body’s extracellular matrix (ECM), based on hyaluronic acid, collagen and laminins. They found that ECM composition radically changed the behaviour of cancer cells and influenced their response to chemotherapy, indicating that the choice of ECM is an important factor in models that try to imitate human disease.
The researchers then added blood vessel-like structures. Blood vessels are important for tumour growth because they supply cells with oxygen and nutrients. They are also the most common route by which tumours spread to other parts of the body. Cancer drugs are also transported to tumours through the bloodstream.
“We saw that the cancer cells responded to the nearby blood vessel, moved rapidly towards it and invaded it, which is the first step in tumour spread. However, the cells behaved very differently depending on the material surrounding them,” Pagella said.
The team then used the blood vessel structure to administer cisplatin, a medicine commonly used to treat the cancer. The type of ECM material also had an impact on how effectively cisplatin killed the cancer cells.
To complete the model, the researchers used stem cells to recreate trigeminal ganglia, the starting point of nerves that are involved in sensation and pain in the mouth and throughout the face. Within a few days, the nerves had grown around the tumours.
“In our three-dimensional system, we saw that tumours in contact with nerves were less likely to invade blood vessels, but at the same time grew larger. Our model enables us to study nerves as an active component of the tumour microenvironment,” said Pagella.
The organ-on-a-chip could be adapted to other solid tumour types in which interactions with surrounding structures and tissues are important, a Linköping announcement said. “Besides supporting studies that increase our understanding of how cancer behaves and is affected by its surroundings, the method could eventually prove useful for applications such as drug screening and testing treatment response,” it added.
The study received funding from, among others, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the European Research Council and the Swedish Foundation for Strategic Research.
The work was published in Proceedings of the National Academy of Sciences.
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