The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer

Nicole Antonio, Marie Louise Bønnelykke-Behrndtz, Laura Chloe Ward, John Collin, Ib Jarle Christensen, Torben Steiniche, Henrik Schmidt, Yi Feng, Paul Martin

Research output: Contribution to journalArticle (Academic Journal)peer-review

93 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2219-2236
Number of pages18
JournalEMBO Journal
Volume34
Issue number17
DOIs
Publication statusPublished - 2 Sep 2015

Bibliographical note

© 2015 The Authors. Published under the terms of the CC BY 4.0 license.

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