Organ-on-a-chip model recreates head and neck tumour microenvironment

Researchers at Linköping University in Sweden, working with colleagues at Politecnico di Milano in Italy, have developed an organ-on-a-chip model that replicates key features of the environment surrounding head and neck tumours.

Described in a study published in Proceedings of the National Academy of Sciences (PNAS), the system incorporates cancer cells, blood vessel-like structures and nerves on a small, postage stamp sized plate.

Solid tumours are complex structures that interact with the tissues around them. Blood vessels supply oxygen and nutrients, while nerves can influence tumour behaviour and contribute to cancer-related pain. Understanding these relationships is important for investigating how cancers grow, spread and respond to treatment. 

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.”

Pierfrancesco Pagella, Senior Associate Professor at Linköping University

 

Modelling blood vessels and surrounding tissue

The researchers developed the model in three stages, beginning with a material designed to replicate the extracellular matrix (ECM). This network of proteins and carbohydrates surrounds cells in the body and provides structural support.

They created an ECM-like material using hyaluronic acid, collagen and laminins, finding that changing its composition substantially altered cancer cell behaviour and influenced how the cells responded to chemotherapy. This highlighted to the researchers the importance of accurately replicating the tumour microenvironment.

Next, the team introduced blood vessel-like structures, which are both important for tumour development and the spread of cancer cells to other parts of the body. They also provide a route through which anticancer medicines can reach tumours.

“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 explains.

The team also used the blood vessel structures to administer cisplatin, a chemotherapy medicine commonly used to treat head and neck cancer. Again, the composition of the ECM influenced how effectively the treatment killed cancer cells.

Investigating the role of nerves

To complete the model, the researchers used stem cells to recreate trigeminal ganglia, structures from which nerves involved in sensation and pain in the mouth and face originate.

Within days, the nerves had grown around the tumours, allowing the researchers to see how nerve interactions influenced cancer behaviour.

“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,” said Pagella. ”Our model enables us to study nerves as an active component of the tumour microenvironment. This is particularly interesting in head and neck cancer, where nerves are involved both in regulating tumour behaviour and aggressiveness, and in cancer-related pain.”

The researchers believe the technology could be adapted to other solid tumour types where interactions with surrounding tissues are important.

Beyond improving understanding of cancer biology, the model could eventually support drug screening and the assessment of treatment responses under controlled laboratory conditions.