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 journalArticlepeer-review

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 RasG12V‐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
Early online date1 Jul 2015
DOIs
Publication statusPublished - 2 Sep 2015

Keywords

  • cancer inflammation
  • cancer surgery
  • live imaging
  • melanoma
  • wound healing

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