Increased PGE2 levels in nonmalignant mucosa adjacent to squamous cell carcinoma of the head and neck

Abstract

Objective: The cyclooxygenases (COX) 1 and 2 are the rate-limiting enzymes of prostaglandin E(2) (PGE(2)) synthesis, and the upregulation of COX-2 has been reported in tumors of different origins. The aim of our study was to quantify the PGE(2) expression in squamous cell carcinoma and surrounding mucosa, to analyze the potential of acetylsalicylic acid (ASA) for reducing PGE(2) levels in these tissues, and to improve our understanding of potential tumor-derived stimulation of surrounding mucosa by PGE(2).

Study design and setting: Intracellular PGE(2) levels in primary head and neck squamous cell carcinoma (HNSCC) and the surrounding mucosa at 1 and 2 cm distance were analyzed ex vivo by ELISA. Subsequently, we treated in vitro tumor and normal mucosal cells from turbinates with recombinant PGE(2) and ASA, and quantified intracellular PGE(2) levels.

Results: We observed high PGE(2) levels in the tumor samples and in tumor-surrounding mucosa. The addition of PGE(2) and arachidonic acid to tumor cell cultures resulted in no further increase in intracellular PGE(2) levels, while ASA reduced PGE(2) levels by up to 40%. In normal epithelial cell cultures, less PGE(2) (6% of that found in the tumor cells) was expressed, but stimulation with PGE(2) resulted in levels comparable to those of the tumor samples.

Conclusion and significance: We conclude that HNSCC and the surrounding mucosa express high levels of PGE(2). This expression is reduced efficiently by ASA. We propose a stimulation of PGE(2) expression in the epithelium surrounding HNSCC by tumor-derived PGE(2) with a potential impact on tumor growth.