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EMBO J. 2015 Sep 2;34(17):2219-36. doi: 10.15252/embj.201490147. Epub 2015 Jul 1.

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

Author information

1
School of Biochemistry, University of Bristol, Bristol, UK.
2
Department of Experimental Clinical Oncology, Aarhus University, Aarhus, Denmark Department of Plastic and Reconstructive Surgery, Aarhus University, Aarhus, Denmark.
3
School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
4
Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
5
Department of Pathology, Aarhus University, Aarhus, Denmark Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
6
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark Department of Oncology, Aarhus University, Aarhus, Denmark henrschm@rm.dk yi.feng@ed.ac.uk paul.martin@bristol.ac.uk.
7
MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK henrschm@rm.dk yi.feng@ed.ac.uk paul.martin@bristol.ac.uk.
8
School of Biochemistry, University of Bristol, Bristol, UK School of Physiology and Pharmacology, University of Bristol, Bristol, UK School of Medicine, University of Cardiff, Cardiff, UK henrschm@rm.dk yi.feng@ed.ac.uk paul.martin@bristol.ac.uk.

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.

KEYWORDS:

cancer inflammation; cancer surgery; live imaging; melanoma; wound healing

PMID:
26136213
PMCID:
PMC4585460
DOI:
10.15252/embj.201490147
[Indexed for MEDLINE]
Free PMC Article

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