The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer.
Bottom Line: 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.
Affiliation: School of Biochemistry, University of Bristol, Bristol, UK.Show MeSH
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Mentions: Since we have previously shown that PGE2 is released by neutrophils and macrophages when recruited to pre-neoplastic cells in unwounded larvae (Feng et al, 2012), we wondered whether this factor might also be, in part, responsible for the wound-inflammation-triggered local proliferation of these cells. To test this, larvae were immersed in either 0.5% DMSO or 10 μM Cox-2 inhibitor NS398 with 0.5% DMSO and the number of pre-neoplastic cells was analysed 2 days post-laser wounding (Fig4A–C). Although the addition of NS398 does not completely block the increase in pre-neoplastic cell number post-wounding, we now see a significant reduction in numbers, such that there is no significant difference between the unwounded DMSO-treated larvae and the wounded NS398-treated larvae, suggesting that the addition of a Cox-2 inhibitor could partially negate the trophic impact of a cancer surgery (Fig4C). 20 μM of synthetic prostaglandin E2 (dmPGE2) was added at the point of wounding and largely rescued the proliferative response in immune-depleted zebrafish larvae (Figs3L and 4G), suggesting that PGE2 derived from immune cells is one contributor towards the trophic factors responsible for the wound-induced increase in proliferation.
Affiliation: School of Biochemistry, University of Bristol, Bristol, UK.