Replacing the need for patient-derived xenografts and matrigel organoid culture as preclinical models for breast cancer

Most cells in your body are surrounded by a matrix of proteins and sugars. Cells interact with these and react to the elasticity and stiffness of the matrix. The extracellular matrix plays a key role in disease progression but is difficult to study in the lab. Studies are often carried out in human cells grown on plastic (2D) which poorly supports matrix interactions. To understand 3D matrix-driven behavior, labs rely on highly variable animal-derived artificial matrices or use animal models, including the growth of human cells transplanted into mice. Although these are more realistic, neither models the complex human tissue matrix well. We need to improve the 3D growth of cells within the laboratory and reduce the need for animal models.

We have developed a fully synthetic, reproducible gel that can mimic the matrix of human tissues. Breast cancer cells, along with other cell types, can be encapsulated and easily grown in the lab. This project aims to develop tools to share our mimics with research scientists throughout the world, providing cheap, functional and robust environments. This will allow researchers to test theories of cancer development, discover new targets for intervention and provide more realistic environments to screen therapeutics. To demonstrate the adaptability of our method we will also modify the gel formulations to (i) work in a fully animal product-free system (ii) to encapsulate breast cancer stem cells.

This project links the group who have developed the hydrogels with one of the world-leading groups researching breast cancer. This will ensure that we can reach and influence the global breast cancer research community and companies developing therapeutics. We will use a combination of on-line training packages and physical workshops to create a reliable way of sharing information. We anticipate significantly reducing the numbers of animals used in xenograft studies whilst also improving the relevance of work carried out in the laboratory.

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Skills and Knowledge Transfer grant

Status:

Not yet active

Principal investigator

Dr Robert Clarke

Institution

The University of Manchester

Co-Investigator

Dr Catherine Merry
Dr Jennifer Ashworth

Grant reference number

NC/T001267/1

Award date:

Jul 2019 - May 2020

Grant amount

£74,983