PUBLICATION
The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer
- Authors
- Antonio, N., Bønnelykke-Behrndtz, M.L., Ward, L.C., Collin, J., Christensen, I.J., Steiniche, T., Schmidt, H., Feng, Y., Martin, P.
- ID
- ZDB-PUB-150703-8
- 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.
Citation
Antonio, N., Bønnelykke-Behrndtz, M.L., Ward, L.C., Collin, J., Christensen, I.J., Steiniche, T., Schmidt, H., Feng, Y., Martin, P. (2015) The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer. The EMBO journal. 34(17):2219-36.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping