Researchers at King's College London have identified a new mechanism by which skin damage triggers the formation of tumours, which could have important therapeutic implications for patients suffering with chronic ulcers or skin blistering diseases.
The study, published today in Nature Communications, highlights an innate sensing of bacteria by immune cells in the formation of skin tumours. This molecular process could tip the balance between normal wound repair and tumour formation in some patients, according to researchers.
Although an association between tissue damage, chronic inflammation and cancer is well established, little is known about the underlying cause. Epidermolysis Bullosa (EB), for instance, is one of several rare inherited skin conditions associated with chronic wounding and increased risk of tumours.
However, this study - funded primarily by the Medical Research Council (MRC) and the Wellcome Trust - is the first to demonstrate that bacteria present on the skin can contribute to the development of skin tumours.
Researchers found that when mice with chronic skin inflammation are wounded they develop tumours at the wound site, with cells of the immune system required for this process to take place. They discovered that the underlying signalling mechanism involves a bacterial protein, flagellin, which is recognised by a receptor (Toll-like receptor 5) on the surface of the immune cells.
Although the direct relevance to human tumours is yet to be tested, researchers have shown that a protein called HMGB1 - found to be highly expressed in mice with chronic skin inflammation - is increased in human patients with Epidermolysis Bullosa (EB). The study found a reduction in HMGB1 levels in mice when the TLR-5 receptor was removed from immune cells. This raises the possibility of future treatments aimed at reducing levels of the flagellin bacterial protein on the skin surface, or targeting the TLR-5 receptor.
Professor Fiona Watt, lead author and Director of the Centre for Stem Cells and Regenerative Medicine at King's College London, said: 'These findings have broad implications for various types of cancers and in particular for the treatment of tumours that arise in patients suffering from chronic ulcers or skin blistering diseases.
'In the context of chronic skin inflammation, the activity of a particular receptor in white blood cells, TLR-5, could tip the balance between normal wound repair and tumour formation.'
Professor Watt added: 'Our findings raise the possibility that the use of specific antibiotics targeting bacteria in wound-induced malignancies might present an interesting clinical avenue.'
For further information please contact Jack Stonebridge, Press Officer at King's College London, on 0207 848 3238 or email firstname.lastname@example.org
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About King's College London
King's College London is one of the top 20 universities in the world (2014/15 QS World University Rankings) and the fourth oldest in England. It is The Sunday Times 'Best University for Graduate Employment 2012/13'. King's has nearly 26,000 students (of whom more than 10,600 are graduate students) from some 140 countries worldwide, and more than 7,000 staff. The College is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £590 million.
King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar.
King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: http://www.
The Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to improving health. We provide more than £700 million a year to support bright minds in science, the humanities and the social sciences, as well as education, public engagement and the application of research to medicine.
About the Medical Research Council
The Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers' money in some of the best medical research in the world across every area of health. Thirty MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms.