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.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Alcolea S,Antón R,Camacho M,Soler M,Alfranca A,Avilés-Jurado FX,Redondo JM,Quer M,León X,Vila Ldoi
10.1194/jlr.M019695subject
Has Abstractpub_date
2012-04-01 00:00:00pages
630-42issue
4eissn
0022-2275issn
1539-7262pii
jlr.M019695journal_volume
53pub_type
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
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journal_title:Journal of lipid research
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doi:
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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doi:
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journal_title:Journal of lipid research
pub_type: 杂志文章
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