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

Antonio, N., Bonnelykke-Behrndtz, M. L., Ward, L. C., Collin, J., Christensen, I. J., Steiniche, T., Schmidt, H., Feng, Y. and Martin, Paul 2015. The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer. EMBO Journal 34 (17) , pp. 2219-2236. 10.15252/embj.201490147

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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 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: European Molecular Biology Organization; Nature Publishing Group
ISSN: 0261-4189
Date of Acceptance: 25 May 2015
Last Modified: 10 Jun 2019 14:04
URI: http://orca-mwe.cf.ac.uk/id/eprint/84226

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