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

• Nicole Antonio ^[1] ; Marie Louise Bønnelykke-Behrndtz ^[2] ; Laura Chloe Ward ^[1] ; John Collin ^[1] ; Ib Jarle Christensen ^[3] ; Torben Steiniche ^[2] ; Henrik Schmidt ^[2] ; Yi Feng ^[4] ; Paul Martin ^[1]
  1. [1] University of Bristol

     University of Bristol

     Reino Unido

     
  2. [2] Aarhus University

     Aarhus University

     Dinamarca

     
  3. [3] University of Copenhagen

     University of Copenhagen

     Dinamarca

     
  4. [4] University of Edinburgh

     University of Edinburgh

     Reino Unido

     

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 34, Nº. 17, 2015, págs. 2219-2236
• Idioma: inglés
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• Resumen

  • 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.