Prostaglandin receptor possible target in Barrett’s–associated adenocarcinoma
MedWire News: Researchers have identified prostaglandin E2 (PGE2) receptors that could be selective targets in the prevention and treatment of adenocarcinoma associated with Barrett’s esophagus.
Their finding that expression of the receptors EP4 and particularly EP2 are increased in the Barrett’s metaplasia–intraepithelial neoplasia–adenocarcinoma sequence offers alternative molecular targets to cyclo-oxygenase 2 (COX-2).
“COX-2 has been seen as a molecular target in the prevention and treatment of esophageal cancer, but… the use of COX-2 selective inhibitors has been associated with serious cardiovascular events, which will prevent their use as chemopreventive agents,” Pilar Jiménez (CIBER Enfermedades Hepáticas y Digestivas, Zaragoza, Spain) and colleagues explain.
PGE2 mediates the effects of elevated COX-2 in esophageal adenocarcinoma and exerts its effects through binding to specific receptors, which differ in structure, binding profiles, and the intracellular signal pathways used.
The researchers assessed the expression of the PGE2 receptors EP1, EP2, EP3, and EP4 in esophageal biopsies from 85 patients with esophagitis, Barrett’s metaplasia, intraepithelial neoplasia, esophageal adenocarcinoma, as well as biopsies of normal esophagus.
All four receptors were expressed in human esophageal tissues. As expected COX-2 protein expression was increased in biopsies from patients with Barrett’s metaplasia, intraepithelial neoplasia, and esophageal adenocarcinoma, and increased according to the severity of the lesion.
But EP2 expression was also increased, with most patients showing moderate intensity staining (degree 2). However, the increase in staining was greater in the early phases of the sequence, with 35.7% of patients with Barrett’s metaplasia and 46.7% of patients with lo-grade intraepithelial neoplasia showing strong staining compared with just 9.1% of patients with adenocarcinoma. Staining for the EP4 receptor was predominantly weak in the patient groups, except in those with esophageal adenocarcinoma, among whom 46.2% showed moderate intensity staining.
There was no significant difference in EP1 expression and EP3 protein levels were markedly decreased along the Barrett’s metaplasia–intraepithelial neoplasia–adenocarcinoma sequence.
The researchers also note in the journal Alimentary Pharmacology and Therapeutics that exposure of the Barrett’s adenocarcinoma cell line OE33 to deoxycholic acid induced EP1, EP2, and EP4 receptor expression. The level was significantly lower compared with COX-2 induction, however.
They conclude: “In addition, to COX-2, EP2, and EP4 receptors could be a selective target in the prevention and/or treatment of the Barrett’s-associated adenocarcinoma.”
The team also highlights the importance of future research to define which EP receptors mediate the physiological processes exerted by PGE2.
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By Lucy Piper