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

Autor: Antonio N; School of Biochemistry, University of Bristol, Bristol, UK., Bønnelykke-Behrndtz ML; Department of Experimental Clinical Oncology, Aarhus University, Aarhus, Denmark Department of Plastic and Reconstructive Surgery, Aarhus University, Aarhus, Denmark., Ward LC; School of Physiology and Pharmacology, University of Bristol, Bristol, UK., Collin J; School of Physiology and Pharmacology, University of Bristol, Bristol, UK., Christensen IJ; Department of Public Health, University of Copenhagen, Copenhagen, Denmark., Steiniche T; Department of Pathology, Aarhus University, Aarhus, Denmark Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Schmidt H; 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., Feng Y; MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK henrschm@rm.dk yi.feng@ed.ac.uk paul.martin@bristol.ac.uk., Martin P; 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.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2015 Sep 02; Vol. 34 (17), pp. 2219-36. Date of Electronic Publication: 2015 Jul 01.
DOI: 10.15252/embj.201490147
Abstrakt: 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.
(© 2015 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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