British scientists who developed an advanced three dimensional (3-D) model of human breast cancer in the test tube, have won a prestigious prize for replacing animal experiments in medical research. The award was made at an event at the House of Lords sponsored by former Minister for Science & Innovation Lord Sainsbury and hosted by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).

The research, which was published in Breast Cancer Research journal [1] was funded by the Dr Hadwen Trust for Humane Research charity which pioneers new techniques to replace animals in medical experiments [2].

Dr Deborah Holliday [3], now based at the Department of Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, and colleagues from Queen Mary's, University of London, have constructed a multi-cellular 3-D model of ductal carcinoma in situ (DCIS), a pre-invasive lesion which is the main precursor to breast cancer and accounts for 20% of all breast cancer. The highly successful, complex model useshuman cells from cancerous and healthy breast tissue donated by volunteers and is set to help replaceexperiments using up to 400 mice per test typically involving implanting tumours, abdominal drug injections and serial 'harvesting' of tumours. [4]

Breast cancer is the most common cancer affecting women in the Western world. Over 45,000 women were diagnosed with breast cancer in the UK in 2005, around 125 women each day [5]. Research has been complicated by the fact that the animal 'models' used for cancer research differ significantly from human cancer. More human-relevant research methods are desperately needed to improve research quality.

The 3-D replacement model accurately replicates what happens at a cellular level in normal and malignant human breast. Containing all the different cell types present in breast tissue, it is physiologically relevant and capable of complex, functional studies including the identification and screening of novel therapeutic targets. [6]

"Winning the NC3Rs prize is an important recognition of the quality of non-animal replacement methods, and the scientific and ethical benefits of replacing animals in medical research." says Wendy Higgins, Dr Hadwen Trust for Humane Research. "Supporting groundbreaking non-animal medical research like this is vitally important because eliminating human and animal suffering is a goal that benefits us all."

The development of a human-relevant model means that researchers can far more reliably investigate the earlier stages of cancer, and its progression, as well as potential new breast cancer treatments.

Dr Deborah Holliday [5] is convinced that non-animal solutions like the 3-D model, are the way forward in breast cancer research.

Says Dr Holliday: "This is an exciting development in both breast cancer research and the replacement of animals so I am thrilled at the award . Understanding how individual cell populations contribute to cancer progression is essential in increasing our understanding of breast cancer and identifying new targets for therapy. Being able to model this in a complex human 3-D culture model provides us with a valuable tool to investigate this without the use of animal experiments."

The event was hosted by the NC3Rs as part of its celebrations to mark the 50th anniversary of Russell and Burch's concept of replacement, reduction and refinement of animal experiments (3Rs). The poster event was held on Wednesday 25th March to demonstrate original 3Rs research from the UK for MPs and Peers. Dr Holliday was awarded £3,000. [8]

Notes

1. Novel multicellular organotypic models of normal and malignant breast: tools for dissecting the role of the microenvironment in breast cancer progression Deborah L Holliday, Kellie T Brouilette, Anja Markert, Linda A Gordon, J Louise Jones. Breast Cancer Research 2009, 11:R3 (19 January 2009). http://breast-cancer-research.com/content/11/1/R3

2. The Dr Hadwen Trust is the UK's leading medical research charity funding exclusively non-animal research techniques to replace animal experiments, benefiting people and animals. http://www.drhadwentrust.org

3. Dr Deborah Holliday, Breast Research Group, Section of Pathology and Tumour Biology, Leeds Institute of Molecular Medicine. Email: D.L.Holliday@leeds.ac.uk Tel: 0113 343 8624

4. In DCIS cells inside some of the ducts of the breast start to become cancerous but are at a stage where they have not yet invaded the rest of the breast.

5. Statistics from Cancer Research UK.

6. Experiments so far with the 3-D model have shown that if the cells which surround invasive tumours (called fibroblasts) are taken from cancer-containing breast tissue, they disrupt structures, giving the cells a disorganised appearance often seen in cancer. However, fibroblasts taken from healthy breast tissue don't cause this disruption.The team has also shown that the 3-D model is accurate enough to establish which specific enzymes play a prominent role in the propagation of tumour cells into healthy breast tissue.

7. Photos of the 3-D model (taken under the microscope) are available on request from the Dr Hadwen Trust.

8. W.M.S. Russell and R.L. Burch (1959) The Principles of Humane Experimental Technique. London, UK: Methuen

9. The NC3Rs was established in 2004 by the government http://www.nc3rs.org.uk

Source
Dr Hadwen Trust