Interaction between head and neck squamous cell carcinoma cells and fibroblasts in the biosynthesis of PGE2.
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.
Laboratory of Angiology, Vascular Biology and Inflammation,  Institute of Biomedical Research (II-B Sant Pau), Barcelona,  Spain.
Sonia
S
Alcolea
Rosa
R
Antón
Mercedes
M
Camacho
Marta
M
Soler
Arantzazu
A
Alfranca
Francesc-Xavier
FX
Avilés-Jurado
Juan-Miguel
JM
Redondo
Miquel
M
Quer
Xavier
X
León
Luis
L
Vila
D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D005591:Chemical Fractionation; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D000071876:Prostaglandin-E Synthases; D011460:Prostaglandins F / Q000378:metabolism; D040081:Protein Array Analysis; D055550:Protein Stability; D011725:Pyridines / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D007093:Imidazoles; D007375:Interleukin-1; D011460:Prostaglandins F; D011725:Pyridines; D017472:Receptors, Interleukin-1; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; C093642:SB 203580; C100006:prostaglandin F1