Interaction between head and neck squamous cell carcinoma cells and fibroblasts in the biosynthesis of PGE 2

Abstract

Prostaglandin (PG)E 2 is relevant in tumor biology, and interactions between tumor and stroma cells dramatically influence tumor progression. We tested the hypothesis that cross-talk between head and neck squamous cell carcinoma (HNSCC) cells and fibroblasts could substantially enhance PGE 2 biosynthesis. We observed an enhanced production of PGE 2 in cocultures of HNSCC cell lines and fibroblasts, which was consistent with an upregulation of COX-2 and microsomal PGE-synthase-1 ( mPGES-1) in fibroblasts. In cultured endothelial cells, medium from fibroblasts treated with tumor cell-conditioned medium induced in vitro angiogenesis, and in tumor cell induced migration and proliferation, these effects were sensitive to PGs inhibition. Proteomic analysis shows that tumor cells released IL-1, and tumor cell-induced COX-2 and mPGES-1 were suppressed by the IL-1-receptor antagonist. IL-1α levels were higher than those of IL-1β in the tumor cell-conditioning medium and in the secretion from samples obtained from 20 patients with HNSCC. Fractionation of tumor cell-conditioning media indicated that tumor cells secreted mature and unprocessed forms of IL-1. Our results support the concept that tumor-associated fibroblasts are a relevant source of PGE 2 in the tumor mass. Because mPGES-1 seems to be essential for a substantial biosynthesis of PGE 2, these findings also strengthen the concept that mPGES-1 may be \a target for therapeutic intervention in patients with HNSCC. Copyright © 2012 by the American Society for Biochemistry and Molecular Biology, Inc.