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标题：Interaction between head and neck squamous cell carcinoma cells and fibroblasts in the biosynthesis of PGE2
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作者：Sonia Alcolea ; Rosa Antón ; Mercedes Camacho 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2012
卷号：53
期号：4
页码：630-642
DOI：10.1194/jlr.M019695
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Prostaglandin (PG)E₂ 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 PGE₂ biosynthesis. We observed an enhanced production of PGE₂ 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 PGE₂ in the tumor mass. Because mPGES-1 seems to be essential for a substantial biosynthesis of PGE₂, these findings also strengthen the concept that mPGES-1 may be \a target for therapeutic intervention in patients with HNSCC.
关键词：arachidonic acid ; cyclooxygenase ; prostaglandin E ; interleukin-1