Nitric oxide synthase-cyclooxygenase interactions are involved in tumor cell angiogenesis and migration.
Nitric oxide (NO), produced by distinct nitric oxide synthase (NOS) isoforms, and prostaglandins generated by expression of cyclooxygenases are important mediators in tumor progression. Previous studies have shown that NO can influence the formation of prostaglandin E2 (PGE2). We provide evidence that NO, derived from iNOS and eNOS activity in LMM3 murine mammary adenocarcinoma cell line, is involved in tumor angiogenesis and in tumor cell migration. LMM3 cells that also stimulate their neovascularization activity and migration liberate high basal amounts of PGE2. There is large amount of evidence that postulates positive regulatory interactions between NOS and cyclooxygenase (COX) isoforms. We here show that, in the LMM3 cell line, while PGE2 exerts a positive modulation on NOS activity, NO closes the loop with a negative feed back on COX activity. We also provide evidence of a positive regulatory effect of protein tyrosine kinases on NOS as well as on COX enzymatic functions affecting tumor induced angiogenesis and cell migration.
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Instituto de Oncología Angel H. Roffo, Departamento de Immunobiología, Universidad de Buenos Aires, Argentina. davel@fmed.uba.ar
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D000818:Animals; D002465:Cell Movement; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology*; D009389:Neovascularization, Pathologic; D019001:Nitric Oxide Synthase / Q000737:chemistry / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011863:Radioimmunoassay; D013696:Temperature
D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D011505:Protein-Tyrosine Kinases; D015232:Dinoprostone