期刊
EMBO JOURNAL
卷 34, 期 17, 页码 2219-2236出版社
WILEY
DOI: 10.15252/embj.201490147
关键词
cancer inflammation; cancer surgery; live imaging; melanoma; wound healing
资金
- Wellcome Trust studentship
- Wellcome Trust Sir Henry Dale Fellowship
- Wellcome Trust Senior Investigator Award
- Cancer Research UK programme
- BBSRC project
- Danish Cancer Society
- EORTC melanoma group
- Korning-foundation
- Arvid Nielssons-foundation
- Wedell-Wedellborgs foundation
- BBSRC [BB/K018027/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/K018027/1] Funding Source: researchfish
- Cancer Research UK [15936] Funding Source: researchfish
- Wellcome Trust [097791/Z/11/Z] Funding Source: researchfish
- Wellcome Trust [097791/Z/11/Z] Funding Source: Wellcome Trust
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 E-2 (PGE(2)). 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.
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