Leukotriene A₄ Signaling, Inflammation, and Cancer

Extract

Chen et al. report in this issue of the Journal that leukotriene A₄ hydrolase (LTA₄H) was overexpressed in 10 rat esophageal adenocarcinomas compared with matched normal tissue samples (1). They also report that LTA₄H was expressed in infiltrating inflammatory cells and in the columnar cells in human esophageal adenocarcinomas. Bestatin, an LTA₄H inhibitor, reduced the incidence of esophageal adenocarcinomas by approximately 30% in a rat esophageal carcinoma model. On the basis of these findings, the authors conclude that LTA₄H overexpression appears to be an early event in esophageal adenocarcinogenesis and is a potential target for the prevention of esophageal cancer. Chen et al. had previously reported that LTA₄H was overexpressed in both human and rat esophageal adenocarcinomas (2). The current results are not too surprising in light of previously published data by this group indicating that nordihydroguaiaretic acid, a lipoxygenase inhibitor, also decreased tumor incidence in this same rat model (3). Cyclooxygenase inhibitors, however, were also effective in reducing the incidence of esophageal adenocarcinomas. Thus, the current study by Chen et al. (1) is a follow-up study evaluating more samples and using an LTA₄H inhibitor in vivo. Others (4) have previously reported that LTA₄H (also known as Grp94) is overexpressed in lung cancer. About a decade ago, this gene was shown to be overexpressed in a rat kidney fibroblast cell line transformed by v-Ki-ras (5), indicating its potential link to cell transformation.