King's College. UK: 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.’