Why did we fund this project?
This award aims to combine two technologies that avoid the use of animal products in in vitro models of breast cancer, improving the relevance of the models and their potential to replace some xenograft studies in mice.
A range of in vivo and in vitro models are used to study breast cancer to reflect different types and stages of the disease. Current in vivo models include xenografts and transgenic models. Xenograft models using patient tissue have low engraftment rates (up to 27%) creating a bias of cancers that are studied. Generating the correct mutation in a genetically engineered mouse model is also inefficient as the majority of animals will not have the mutation of interest. These models can be replaced using 3D in vitro models, however these require animal-derived matrices, such as collagen or Matrigel, to sustain the cellular phenotype. Professor Cathy Merry (Co-Investigator, University of Nottingham) has developed a customisable synthetic peptide hydrogel with NC3Rs funding. By adding various extracellular matrix components, such as proteins or sugars, in specific quantities the hydrogel can be composed to represent the environment of a breast cancer tumour in a patient.
To increase the clinical relevance of the hydrogel model, Professor Valerie Speirs and colleagues will combine this technology with their previously developed PerfusionPal platform, also developed with NC3Rs funding. This uses a high-density liquid “blood substitute” to constantly perfuse growing breast cancer cells enabling delivery of therapeutics as if they were administered intravenously creating a vascularised human 3D cell culture system for the study of breast cancer.
This award was made in collaboration with Cancer Research UK.
Breast cancer is the most common cancer affecting women. Scientists use a range of models to study this in the laboratory. This includes growing cells on plastic dishes or using animal models to mimic how breast cancer behaves. Neither model is ideal; growing cells on plastic is very different from how cells exist in the human body, while the animals used to mimic breast cancer are usually mice, which are very different from humans. We wish to implement a closer-to-patient model of breast cancer. This still uses cells growing in the laboratory, but these are growing in a way that is more similar to how they are in the human body. The cells grow in an engineered three-dimensional matrix developed with NC3Rs funding. Currently, this three-dimensional environment contains animal-derived substances.
In this project we wish to change the three-dimensional environment to make it completely free of any animal products. We can do this using a substance called a hydrogel. We can add different substances to the hydrogel to make it the same as the environment in which breast cancer cells grow in the body. Once we have achieved this we will make this environment closer still to how cancer cells are in the body. In the body cancer cells have a blood supply which allows them to receive a continuous flow of nutrients required to keep them alive. This is how drugs designed to kill cancer cells are also delivered. This is hard to achieve in the laboratory.
We have overcome this by using an artificial blood substitute which we will introduce into our three-dimensional environment. This will produce a breast cancer model which has many similarities to how breast cancer cells grow in the human body, which we will be able to use routinely in our own labs. We want as many scientists as possible to know about this model and be able to use this, so we will organise training events where scientists from all over the UK can receive practical hands-on training in our technology so that are confident to start using this in their own labs. Finally, as university academics we are responsible for training the next generation of scientists so will introduced this technology into our teaching through lectures and practical sessions.