The wound inflammatory response exacerbates growth of pre‐neoplastic cells and progression to cancer. (1st July 2015)

• Record Type: Journal Article
• Authors: Antonio, Nicole; Bønnelykke‐Behrndtz, Marie Louise; Ward, Laura Chloe; Collin, John; Christensen, Ib Jarle; Steiniche, Torben; Schmidt, Henrik; Feng, Yi; Martin, Paul
• Is Part Of: EMBO journal. Volume 34:Number 17(2015)
• Page Start: 2219
• Page End: 2236
• Publication Date: 2015-07-01
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201490147
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main" id="embj201490147-abs-0001"> <title>Abstract</title> <p>There is a long‐standing association between wound healing and cancer, with cancer often described as a "wound that does not heal". However, little is known about how wounding, such as following surgery, biopsy collection or ulceration, might impact on cancer progression. Here, we use a translucent zebrafish larval model of Ras^G12V‐driven neoplasia to image the interactions between inflammatory cells drawn to a wound, and to adjacent pre‐neoplastic cells. We show that neutrophils are rapidly diverted from a wound to pre‐neoplastic cells and these interactions lead to increased proliferation of the pre‐neoplastic cells. One of the wound‐inflammation‐induced trophic signals is prostaglandin E₂ (PGE₂). In an adult model of chronic wounding in zebrafish, we show that repeated wounding with subsequent inflammation leads to a greater incidence of local melanoma formation. Our zebrafish studies led us to investigate the innate immune cell associations in ulcerated melanomas in human patients. We find a strong correlation between neutrophil presence at sites of melanoma ulceration and cell proliferation at these sites, which is associated with poor prognostic outcome.</p> </abstract>