ZFIN ID: ZDB-PUB-150703-8
The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer
Antonio, N., Bønnelykke-Behrndtz, M.L., Ward, L.C., Collin, J., Christensen, I.J., Steiniche, T., Schmidt, H., Feng, Y., Martin, P.
Date: 2015
Source: The EMBO journal   34(17): 2219-36 (Journal)
Registered Authors: Feng, Yi, Martin, Paul
Keywords: cancer inflammation, cancer surgery, live imaging, melanoma, wound healing
MeSH Terms:
  • Animals
  • Cell Proliferation
  • Humans
  • Inflammation/genetics
  • Inflammation/immunology
  • Inflammation/pathology
  • Melanoma/genetics
  • Melanoma/immunology*
  • Mutation, Missense
  • Neoplasms, Experimental/genetics
  • Neoplasms, Experimental/immunology*
  • Neoplasms, Experimental/pathology
  • Neutrophils/immunology
  • Neutrophils/pathology
  • Precancerous Conditions/genetics
  • Precancerous Conditions/immunology*
  • Precancerous Conditions/pathology
  • Wounds and Injuries/genetics
  • Wounds and Injuries/immunology*
  • Wounds and Injuries/pathology
  • Zebrafish/genetics
  • Zebrafish/immunology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/immunology
  • ras Proteins/genetics
  • ras Proteins/immunology
PubMed: 26136213 Full text @ EMBO J.
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.