Bacterial input to wound-associated skin cancer - Printable Version
+- Biotechnology Forums (https://www.biotechnologyforums.com)
+-- Forum: Information (https://www.biotechnologyforums.com/forum-16.html)
+--- Forum: News (https://www.biotechnologyforums.com/forum-15.html)
+--- Thread: Bacterial input to wound-associated skin cancer (/thread-6746.html)
Bacterial input to wound-associated skin cancer - mtwalsh01 - 01-10-2015
Binding of a bacterial protein by a white blood cell receptor at the site of wounds associated with chronic skin inflammation can tip the balance from wound healing to tumour formation. That is a major finding of a study published today in the journal Nature Communications from researchers in King's College London. The results of this mouse study may have important ramifications for therapies for patients suffering from chronic ulcers or skin blistering diseases.
It has been previously established that there is a link between chronic inflammation, tissue damage and tumour formation, however underlying mechanisms are not well understood. The current study is the first to show that bacteria on the skin could contribute to the formation of skin tumours. In the study, the researchers examined wounds in mice with chronic skin inflammation. They observed that tumours formed at the wound site, which depended on the presence of immune cells. The underlying signalling mechanism involved a pattern recognition receptor called Toll-like receptor 5 (TLR-5) on the surface of immune cells. TLR-5 recognises and binds to the bacterial flagellin protein, a protein monomer containing highly conserved regions which makes up the bacterial flagella, found on most motile bacteria.
The direct relevance of the findings to human skin cancer has yet to be investigated, however in an inherited chronic skin condition in humans called Epidermolysis Bullosa (EB), a protein called High mobility group box 1 (HMGB1), which is a nuclear protein involved in transcriptional regulation, is increased. HMGB1 is also increased in mice with chronic skin inflammation and in the current study, removal of TLR-5 from immune cells caused a reduction in HMGB1 levels in mice. These results suggest that therapies involving reduction of bacterial flagellin protein on the skin surface or targeting of TLR-5 could be effective in prevention of tumours in patients with chronic skin conditions.
Lead author 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…Our findings raise the possibility that the use of specific antibiotics targeting bacteria in wound-induced malignancies might present an interesting clinical avenue.'
Reference: Hoste E et al. Innate sensing of microbial products promotes wound-induced skin cancer. Nature Communications 6, Article number: 5932; doi:10.1038/ncomms6932