title: Tumor cells induce COX-2 and mPGES-1 expression in microvascular endothelial cells mainly by means of IL-1 receptor activation.
abstract: Prostaglandin (PG) E(2) plays a key role in immune response, tumor progression and metastasis. We previously showed that macrovessel-derived endothelial cells do not produce PGE(2) enzymatically because they do not express the inducible microsomal PGE-synthase-1 (mPGES-1). Nevertheless, differences between macro- and micro-vessel-derived endothelial cells regarding arachidonic acid (AAc) metabolism profile have been reported. The present work was conducted to evaluate the expression of PGE(2)-pathway-related enzymes in human microvascular endothelial cells (HMVEC) in culture and to test the hypothesis that the tumor cell-HMVEC cross talk could increase mPGES-1 expression in HMVEC. We treated HMVEC in culture with human recombinant IL-1β. IL-1β induced PGE(2) release and COX-2 and mPGES-1 expression in terms of mRNA and protein, determined by real-time PCR and immunoblotting, respectively. HMVEC constitutively expressed mPGES-2 and cytosolic PGES (cPGES) and the IL-1β treatment did not modify their expression. PGE(2) synthesized by HMVEC from exogenous AAc was linked to mPGES-1 expression. Immunohistochemistry analysis confirmed mPGES-1 expression in microvessels in vivo. COX-2 and mPGES-1 were also induced in HMVEC by the conditioned medium from two squamous head and neck carcinoma cell lines. Conditioned medium from tumor cell cultures contained several cytokines including the IL-1β and IL-1α. Tumor cell-induced COX-2 and mPGES-1 in HMVEC was strongly inhibited by the IL-1-receptor antagonist, indicating the important implication of IL-1 in this effect. HMVEC could therefore contribute directly to PGE(2) formed in the tumor. Our findings support the concept that mPGES-1 could be a target for therapeutic intervention in patients with cancer.
authors.affiliation: Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain.
authors.forename: Kelly
authors.initials: K
authors.lastname: Casós
authors.forename: Laura
authors.initials: L
authors.lastname: Siguero
authors.forename: María-Teresa
authors.initials: MT
authors.lastname: Fernández-Figueras
authors.forename: Xavier
authors.initials: X
authors.lastname: León
authors.forename: María-Pilar
authors.initials: MP
authors.lastname: Sardá
authors.forename: Luis
authors.initials: L
authors.lastname: Vila
authors.forename: Mercedes
authors.initials: M
authors.lastname: Camacho
mesh_terms: D002291:Carcinoma, Papillary / Q000098:blood supply / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053582:Interleukin-1alpha / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D000071876:Prostaglandin-E Synthases; D011453:Prostaglandins / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000098:blood supply / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; C507763:IL1RN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D011453:Prostaglandins; D017472:Receptors, Interleukin-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; C000605863:PTGES2 protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone