A recent study, published in Nature Communications by King’s College London researchers, has identified a novel mechanism associated with skin damage that initiates tumor formation.
The researchers describe an innate detection of bacteria by the cells of the immune system during the development of skin tumors. This kind of delicate molecular mechanism can disturb the balance between normal wound repair and tumor formation.
There have been previous studies describing a link between tissue damage, chronic inflammation and cancer, however not much is known about the actual cause behind these occurrences.
In this study, the authors successfully demonstrated that the bacteria present on the skin have a major role in the initiation of skin tumors.
Using mice models of chronic skin inflammation, the researchers observed that upon wounding, these animals start to develop tumors at the site of the wound, a process that requires the recruitment of immune cells.
Importantly, they found that the signaling mechanisms behind this process involve flagellin, a bacterial protein that is recognized by the Toll-like receptor 5 (TLR5) present on the surface of immune cells. Furthermore, a protein called HMGB1, which is expressed at high levels in mice suffering from chronic skin inflammation, is significantly increased in humans suffering from Epidermolysis Bullosa, a rare skin disease that is associated with an increased risk of tumor development.
Upon downregulation of the TLR5 receptor in mice immune cells, the team observed a significant reduction of the levels of HMGB1 in these animals.
These results raise the possibility of targeting the TLR-5 receptor present in immune cells as a potential future therapy.
Study lead author Professor Fiona Watt, Director of the Centre for Stem Cells and Regenerative Medicine at King’s College London, said in a news release, “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. Our findings raise the possibility that the use of specific antibiotics targeting bacteria in wound-induced malignancies might present an interesting clinical avenue.”
