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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Skills and Knowledge Transfer grant

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

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At a glance

Completed
Award date
July 2019
Grant amount
£75,591
Principal investigator
Dr Robert Clarke
Institute
The University of Manchester

R

  • Reduction
  • Replacement

Overview

Why did we fund this project?

This award aims to adapt a synthetic hydrogel for serum-free culture that can be used to support the growth of breast cancer stem cells in vitro rather than using xenograft mouse models for some studies.

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, however, those using patient tissue have low engraftment rates creating a bias of cancers that are studied. Some studies using mouse xenograft models can be replaced using 3D in vitro approaches, but these currently 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.

Dr Robert Clarke is part of the Manchester Breast Centre, and he is using his networks to facilitate take up of the hydrogel model through the development of, online resources including videos, written protocols, FAQs and support pages. These will focus on culturing breast cancer cell lines, cells isolated from xenograft tumours and cells taken directly from patients with different molecular subtypes of breast cancer, including protocols for serum-free culture and breast cancer stem cell growth.

This award was made in collaboration with Cancer Research UK.

Publications

  1. Ashworth JC et al. (2020). Preparation of a User-Defined Peptide Gel for Controlled 3D Culture Models of Cancer and Disease. J. Vis. Exp. 166:e61710. doi: 10.3791/61710
  2. Ashworth JC et al. (2020). Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro. Matrix biology 85-86:15-33. doi: 10.1016/j.matbio.2019.06.009