|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.
|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|
|PubMed:||26136213 Full text @ EMBO J.|
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.
ABSTRACTThere 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.