National Antivisection Society
Research projects 2001 - Cancer
In vitro model for the study of liver metastasis from cancer of the colon
Dr Bird of Sheffield University is the first researcher in the UK to use human tissue models for the study of liver metastasis, where cells from an original cancer tumour spread to the liver and new tumours start to grow. Colorectal cancer (cancer of the lower part of the alimentary canal, or digestive tract) is the second most common malignant cancer in the UK with approximately 29,000 new cases each year. About 15,000 people die each year from cancer of the colon, mostly as a result of tumours developing in the liver.
With the support of the Lord Dowding Fund, Dr Bird is investigating the interaction between liver endothelial cells and tumour cells. This will allow better understanding of how tumours spread from the colon to the liver so that a suitable therapy may be developed. Animal cells and unsuitable human umbilical cord cells have previously been used for these investigations by other researchers. However, at the Royal Hallamshire Hospital where Dr Bird is based, partial hepatectomy operations are regularly carried out as treatment for metastatic liver disease, where sections of the liver containing tumours are removed from the patient. Due to the structure of the liver whole sections must be cut away rather than just the tumour, thereby giving Dr Bird access to the excess healthy liver tissue literally seconds after it is removed from the patient.
Using the liver tissue, Dr Bird has established a bank of cultured liver cells, which may now be used to research the mechanisms of tumour formation. Previously, Dr Bird established an in vitro model of the gallbladder for cancer research investigations. The Home Office has identified research for metastasis in cancer as involving substantially severe animal models in human diseases. It is therefore hoped that by setting the precedent in the UK, of using human tissue to study liver metastases, Dr Bird will encourage other researchers to follow suit.
In vitro assay of angiogenesis inhibitors for the treatment of cancer.
Dr Claire Lewis and her PhD student, Carolyn Bootle-Wilbraham of the University of Sheffield Medical School, have developed a novel in vitro assay, using cultured human cell lines to test the effects of a set of protein molecules, found in tumours, on angiogenesis.
Small tumours must develop a blood supply for themselves if they are to grow beyond 1-2mm in diameter. This process is called ‘angiogenesis’ and the new blood vessels pushing into the tumour mass from the surrounding normal tissue provide the oxygen and nutrients needed for tumour growth and spread. The protein-rich ‘glue’ that holds cells together in tumours (ie the extracellular matrix) helps to control tumour angiogenesis and a number of new potential anti-cancer drugs (eg angiostatin and endostatin) have been used to mimic the angiogenesis-inhibiting effects of small proteins found naturally in the matrix. Blocking the blood supply to a tumour would cause it to shrivel and die.
Traditionally, mice are used for cancer research, despite the fact that mice and humans generally suffer from different types of cancer. The Lord Dowding Fund is supporting Dr Lewis’ research to use human cells, which is of direct clinical relevance to human cancers.
Additionally, a Lord Dowding Fund equipment grant will allow Dr Lewis’ research team to isolate human endothelial cells (from blood vessels derived from surgically-removed tissues), analyse their protein expression in vitro, and microscopically observe their activity in forming vessels in vitro. This will assist in advancing a range of non-animal research projects, particularly in the fields of breast and ovarian cancer research.
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