Tumor cells induce COX-2 and mPGES-1 expression in microvascular endothelial cells mainly by means of IL-1 receptor activation
Por:
Casós K., Siguero L., Fernández-Figueras M.-T., León X., Sardá M.-P., Vila L., Camacho M.
Publicada:
1 ene 2011
Resumen:
Prostaglandin (PG) E2 plays a key role in immune response, tumor progression and metastasis. We previously showed that macrovessel-derived endothelial cells do not produce PGE2 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 PGE2-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-1ß IL-1ß induced PGE2 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-1ß treatment did not modify their expression. PGE2 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-1ß and IL-1a. 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 PGE2 formed in the tumor. Our findings support the concept that mPGES-1 could be a target for therapeutic intervention in patients with cancer. © 2011 Elsevier Inc.
Filiaciones:
Casós K.:
Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain
Siguero L.:
Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain
Fernández-Figueras M.-T.:
Pathology Department, Hospital Germans Trias i Pujol, Universitat Autónoma de Barcelona, Spain
León X.:
Otorhinolaryngology Department, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain
Sardá M.-P.:
Haematology Department, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain
Vila L.:
Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain
Camacho M.:
Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain
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