Activity of the leukotriene pathway in Barrett’s metaplasia and oesophageal adenocarcinoma

Abstract

Leukotriene (LT) B(4) is a lipid inflammatory mediator implicated in tumorigenesis in animal models of Barrett's oesophagitis, but little is known about the cysteinyl-leukotrienes (LTC(4), LTD(4), LTE(4)), which have distinct inflammatory and tumorigenic actions in other tissues. We recently showed that the terminal enzymes for the synthesis of both LT families are highly expressed in human oesophageal adenocarcinoma (OA) tissues. This study therefore examined the capacity of Barrett's metaplasia (BM) and OA tissues to synthesise LTs in vitro. Oesophageal biopsies from patients with BM (n=14), high-grade dysplasia (n=2), OA (n=11), and squamous control tissues (n=11) were cultured with calcium ionophore A32187 (2μM) for 60min. LTB(4) and cysteinyl-leukotrienes were extracted and measured by specific enzyme immunoassays. Levels of LTB(4) and cysteinyl-leukotrienes were 8.6-fold (P<0.01) and 2.4-fold (P<0.02) higher, respectively, in OA tissues than in squamous control tissues, but levels in BM tissues (n=14) were not altered. Production of the two LT families correlated across all tissue types (r=0.62, p<0.00005). Increased synthesis of LTB(4) and cysteinyl-leukotrienes has not previously been shown in human OA tissue and our results may indicate a role of these lipids in Barrett's disease progression.