Building an adipose-rich tumour microenvironment model to study fat-cancer cross-talk
A cell culture model will allow Evie Gruszyk at Sheffield Hallam University an opportunity to understand colorectal cancer without the need to use mice.
SUPERVISOR: Dr Nicholas Peake – Sheffield Hallam University
STUDENT: Ms Evie Gruszyk
There is a very clear link between fat and diseases that affect the colon. Particularly, fat build-up around the colon carries an increased risk of developing colon cancer, and our current research is investigating how communication between fat tissue and cells of the colon cause this. However, working with fat is difficult because fat cells are hard to grow in the large numbers needed for complex experiments, which means that confirmation of any interesting results is often done in mice.
This project aims to build a model of fat tissue using a unique human cell line that has been found to grow prolifically, expanding on a model established in our lab which allows us to grow cancer cell clusters in a gel surrounded by normal cells to mimic the physiological cancer environment. Building this model will provide us with a resource that, in the short-term, will enable us to study how interactions between the fat tissue and the cancer cells determine cancer growth, preventing the need to use mice to observe these interactions in a physiological setting. If successful, we aim to use this model for our current and future projects, with the hope that this approach can be disseminated into the wider scientific community as a viable replacement to using animal experiments for studying fat-cancer interactions.
Cancer research is reliant on animals because it requires understanding of a complex multi-cellular tumour micro-enviroments (TME); Mouse models such as Balb/c mice are commonly used. Much recent work has been dedicated to develop in vitro TME mimics, but adipose tissue is difficult to work with since primary cells can be slow growing, and cell lines are not widely available. A 2008 survey showed an approximate doubling in number of adipose tissue studies using mice per year1. Our use of SGBS cells aims to remove the need for murine models to study adipocyte behaviour.
Our research aims to investigate EVs in the TME, focussing on adipocytes. Mouse models are frequently used to confirm the effects of EVs observed in simple culture models. Procedures are usually classified as mild (eg intraperitoneal injection), though monitoring of discomfort is necessary when tumour growth is involved. A recent UK study of EVs targeting the TME using wild type CD-1 and transgenic mice (Rab27-deficient) detailed over 40 animals, not including control experiments mentioned but not elaborated in the report. Our own research is at a point where we need to confirm that EVs influence adipocyte behaviour in a TME model. A similar study size of 40 mice would allow experiments to compare obese to normal animals (ApoE knockout vs wild type), however if this work is successful, we aim for this model to replace the need for these experiments in our immediate work, and to disseminate this approach more widely in the longer term.
REFERENCES: 1) Patrick CW et al (2008). Animal models for adipose tissue engineering. Tissue Eng part B Rev 14: 167-78.; 2) Webber JP et al (2015). Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes. Oncogene 34: 290-302.