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 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 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, 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."
The paper, Innate sensing of microbial products promotes wound-induced skin
cancer, is published in Nature.