Using this discovery, it is hoped that the scientists at Bristol University can target the tumour with drug therapies that switch off the survival mechanism, causing the tumour to self-destruct.
The research was funded by Cancer Research UK and is published online today (14 January 2007) in Nature Cell Biology.
Bowel cancer is the second most common cause of cancer deaths in the United Kingdom. Every year in the UK, around 35,000 people are diagnosed with bowel cancer with about 17,000 people dying from the disease.
Team leader, Professor Chris Paraskeva, explained: “We believe it is essential to understand the survival strategies of cancers as they grow, and how they develop resistance to treatment therapies. These cancers are incredibly smart and constantly adapt to their environment in order to survive – we have just got to be smarter. We hope to use this new information to try and interfere with the tumour’s survival tactics and thereby kill it off.”
Normal cells have a natural cycle of growth that eventually leads to cell suicide. But bowel cancer cells characteristically produce an excess of a protein called Beta Catenin which links with a preferred-partner protein (TCF) to stimulate uncontrolled growth.
As the tumour grows, the existing blood supply becomes inadequate and the tumour cells face death through starvation due to a lack of oxygen and nutrients. In a survival tactic, the ‘smart’ cells halt their growth and produce a new protein called HIF-1 which allows them to grow new blood vessels to feed the enlarged tumour.
The Bristol team’s key finding was that when the growing tumour cells ‘sense’ they are deprived of oxygen and nutrients, Beta Catenin leaves its preferred binding protein, TCF, and binds with the new protein (HIF-1) to form a chemical messenger, further stimulating a new blood supply for the tumour. The new blood supply now offers a fresh source of oxygen and nutrients and a direct route to other bodily organs.
Professor Paraskeva added: “Standard chemotherapy is largely aimed at stopping cell growth and inducing tumour cells to commit cell suicide. Our improved understanding of the protein pathways in cell growth and cell survival affords more opportunity for developing better therapies with which to target the tumour.”
Professor John Toy, Cancer Research UK’s medical director, said: “Bowel cancer is one of the most common cancers in Britain, so research aimed at reducing this toll is vitally important.
“This discovery adds to our understanding of how bowel cancer cells survive when their oxygen and food supplies become severely reduced, and could lead to new cancer treatments. We look forward to seeing the team’s research progress in further laboratory studies and hope eventually to see it translate to clinical trials in patients.”