Why did we fund this project?
This award aims to replace mice in breast cancer metastasis studies by adapting a tissue-on-a-chip device to model cancer colonisation in murine liver tissue.
The spread of cancer cells by metastasis causes the majority of breast cancer deaths in the UK. Metastasis research typically uses longitudinal studies in mice using either implanted cancerous patient tissue or genetically engineered models. These studies require large groups of mice as animals must be culled at specific time points to assess the extent of cancer cell colonisation. Current in vitro models do not accurately replicate the complexity of the tumour microenvironment, either because they lack multiple cell types, or require cancer cells to be seeded directly on top of the tissue, which is not representative of metastasis in vivo. Professor John Greenman and Dr Victoria Green (Co-Investigator) have previously developed a tissue-on-a-chip model, with NC3Rs funding, where tumour biopsy tissue is cultured in a microfluidic device. The tissue encompasses the complexity of the tumour microenvironment and the inclusion of microfluidics replicates blood flow.
In collaboration with Dr Rachel Eyre, John and Victoria will adapt the tissue-on-a-chip device for liver metastasis studies of breast cancer. The technology will be transferred to Rachel’s laboratory at the University of Manchester where she will perfuse a human breast cancer cell line into the chip to colonise murine liver tissue.
This award was made in collaboration with Cancer Research UK.
Breast cancer kills over 11,000 women each year in the UK. Virtually all of these women die because their breast cancer cells travel to other organs within the body such as the liver, lungs, bones and brain, where they grow into new tumours and stop the organs from working. Therefore, one way to stop women dying from breast cancer is to prevent breast cancer cells from growing in other organs. Currently, however, we do not understand how breast cancer cells move to and grow in other organs, so we are not able to prevent it with drugs.
Most studies trying to understand how breast cancer cells grow in different organs take place in mice. However this is not an ideal way to study the process, as it is very difficult to watch cancer cells growing inside a mouse. To get around this, large numbers of mice are used for each experiment with some being killed at different time points and the cancer cell spread to other organs then determined. This uses a lot of mice, and still does not allow us to see exactly what happens when cancer cells are growing in these organs.
Replicating the growth of breast cancer cells in other organs in a laboratory dish would be a way to better understand this process, whilst also reducing the number of mice used in research. Previous work has attempted to do this, however the laboratory systems which have been created lack the complexity of cancer cell growth seen in patients, so uptake amongst researchers has been low.
We have identified a model already in use which has the potential to be used to study breast cancer growth in other organs. This model has been developed at the University of Hull, and is called "tissue-on-a-chip". Tissue-on-a-chip involves taking a small amount of tissue from either a mouse or a human, and keeping it alive in a glass or polymer chip constantly supplied with flowing nutrients. These chips have previously been used to study both normal tissue and tumour tissue, and here we propose to study how breast cancer cells grow in other organs. Tissue from liver, a common site for breast cancer spread, will be placed inside the chips, and then cancer cells from breast tumours will be slowly flowed across and allowed to bind to and invade the liver. This will be monitored using powerful microscopes.
We believe that the successful development of this model could be of great use to scientists working to understand how cancer spreads. We have therefore designed this project firstly to adapt the technology for study breast cancer cells growing in other organs, and secondly to showcase its potential to other scientists. To adapt the tissue-on-a chip technology to study cancer spread we will transfer it to the University of Manchester, where we can use world-class facilities to watch cancer cells as they grow. We will also demonstrate how this technology can be used to test drugs to prevent cancer cells growing in other organs by adding different drugs, and seeing if we can prevent cancer cells from growing. As this technology is being established, we will begin discussions with other scientists across the UK to ensure that people know about this model, and will actively promote the benefits to their research alongside significantly reducing number of mice used in research.
Principal investigatorProfessor John Greenman
InstitutionUniversity of Hull
Co-InvestigatorDr Victoria Green
Dr Rachel Eyre