title: Prostanoids in tumor angiogenesis: therapeutic intervention beyond COX-2.
abstract: Prostanoids regulate angiogenesis in carcinoma and chronic inflammatory disease progression. Although prostanoid biosynthetic enzymes and signaling have been extensively analyzed in inflammation, little is known about how prostanoids mediate tumor-induced angiogenesis. Targeted cyclooxygenase (COX)-2 inhibition in tumor, stromal and endothelial cells is an attractive antiangiogenic strategy; however, the associated cardiovascular side effects have led to the development of a new generation of nonsteroidal anti-inflammatory drugs (NSAIDs) acting downstream of COX. These agents target terminal prostanoid synthases and prostanoid receptors, which may also include several peroxisome proliferator-activated receptors (PPARs). Here, we discuss the role of prostanoids as modulators of tumor angiogenesis and how prostanoid metabolism reflects complex cell-cell crosstalk that determines tumor growth. Finally, we discuss the potential of new NSAIDs for the treatment of angiogenesis-dependent tumor development.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Chemistry 2, Karolinska Institute, S-171 77 Stockholm, Sweden. Dolores.Salvado-Duro@ki.se
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Salvado
authors.forename: Arántzazu
authors.initials: A
authors.lastname: Alfranca
authors.forename: Jesper Z
authors.initials: JZ
authors.lastname: Haeggström
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Redondo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000503:physiopathology; D011453:Prostaglandins / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D051546:Cyclooxygenase 2