Cancer cells go crazy in a specially designed incubator

Imagine a forest fire, and you will have some idea of the raging power behind the spread of cancer cells.

For some unknown reason, a fire starts in a small bush. Once this bush is burning fiercely, the flames spread from the place where the fire started to a neighbouring bush and then to something else – maybe to tinder-dry grass in a small glade bordering on a pine forest. Then, you’re in deep trouble.

This exact same principle is behind the spread of metastatic tumours, which are both difficult to treat and the cause of most cancer patient deaths.

First, there is the original tumour – the fire starter. Once this has had the chance to grow for some time it begins to send cancer cells to other parts of the body. These pathogenic cells then establish new tumours which, in turn, emit more cancer cells – and so it continues.

It is of great value to cancer researchers to understand the details of the process that initiates and drives metastatic tumour formation. However, this is difficult for several reasons, one being that many of the tests and observations researchers would like to perform cannot be conducted in animal models or conventional cell culture systems.

A team of scientists from the Biotech Research & Innovation Centre (BRIC) at the University of Copenhagen have shown that there are other ways of tackling the issue.

Together with clinical researchers from hospitals in the Capital Region of Denmark, they have developed a technique – a model system – that mimics in a special “box” the process that leads to formation of metastatic tumours. Their work, funded by the Lundbeck Foundation and the Danish Cancer Society, among others, was recently published in the scientific journal Advanced Healthcare Materials.

Lungs and livers of mice

The cells in our body form a kind of scaffold that gives tissue structure. This scaffold – the extracellular matrix (ECM) – is part of the body’s connective tissue, and the scaffolding binds cells together.

The same applies in other mammals, such as mice – and the BRIC researchers made use of this fact. They succeeded in manufacturing ECM scaffolds from murine livers and lungs.

It was no coincidence that the researchers decided to use livers and lungs. Cancer occurring in these two organs tends to spread via metastatic tumours.

The two ECM scaffolds created by the research group were placed in a box. This box provides a constant circulation of nutrition, among other things, and by introducing cancer cells, researchers can monitor how the sick cells metastasise and modify the ECM scaffold.

The process this enables us to study is equivalent to the formation of metastatic tumours in humans with cancer, and it gives researchers the opportunity to monitor in real-time both communication between metastasising cancer cells and the physical result of the gradual ravage of these sick cells.

“This can help us identify and direct therapeutic strategies towards the factors that are a prerequisite for metastasis. We can study how cancer cells react on the extracellular matrix and how these cells modify the matrix to suit their needs,” says Assistant Professor Alejandro Mayorca Guiliani.

Guiliani is a member of Professor Janine Erler’s research group at BRIC, and he is the scientist who designed the model system.

Janine Erler, who received the Lundbeck Foundation Young Investigator Prize in 2017, spearheaded this research project.