Replacing in vivo models with the Quasi vivo system to investigate metastatic site priming by tumour cells

Why did we fund this award?

This award aims to replace mice in some breast cancer metastasis studies by adapting an in vitro method of co-culturing multiple cell types to investigate signaling events that prime secondary tumour formation.

The spread of cancer cells by metastasis causes the majority of breast cancer deaths in the UK. Metastasis research typically involves injecting cells from patients or cell lines to determine where secondary tumours form in the animal. These longitudinal studies require large groups of mice as animals are culled at specific time points to assess the extent of cancer cell colonisation. Professor Arti Ahluwalia (Co-Investigator) has previously established the Quasi vivo system, an interconnected cell culture flow system in which cells are maintained in individual chambers with media flowing through the whole system, such that cellular factors released at one site, pass between chambers.

Dr Hannah Harrison will adopt and adapt the in vitro method for her research, culturing breast cancer cells with other cell types from major sites of breast cancer metastasis, including bone, liver and lung cells.

This award was made in collaboration with Cancer Research UK.

Most breast cancer deaths result from metastasis and there is, therefore, an urgent need to understand the complex sequence of events that leads to recurrence. We hypothesise that the primary tumour influences the potential metastatic sites by signalling to them and directing them to change their environments making them suitable for the cancer cell's arrival. We will develop an in vitro method to model niche priming in which we can investigate the interactions between primary breast cancer cells and the typical sites of metastasis including bone, brain, liver and lung. We will use the Quasi vivo system in which cells from each site can be cultured in separate but connected chambers between which medium will flow constantly allowing signals released at one site to reach the others. We will identify the best culture conditions for our different cell types within the system by assessing different media composition, flow rates and cell density. We will then co-culture our breast cancer cells and distant site cells (Fibroblasts, osteoblasts, lung epithelium, hepatocytes and endothelial cells) and assess whether we can see changes in growth, survival and behaviour of each cell population.

This work will contribute to the NC3Rs aims to reduce and replace animal models as it will provide an alternative to rodent models of metastasis which will be applicable in cancer research.

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Skills and Knowledge Transfer grant

Status

Pending start

Institution

University of Manchester

Grant reference number

NC/W000792/1

Award date

Jun 2021 - Jun 2022

Grant amount

£75,381 (co-funded with CRUK)