title: The role of tumour-derived iNOS in tumour progression and angiogenesis.
abstract: BACKGROUND
  Progressive tumour growth is dependent on the development of a functional tumour vasculature and highly regulated by growth factors and cytokines. Nitric oxide (NO) is a free radical, produced both by tumour and host cells, and functions as a signalling molecule downstream of several angiogenic factors. Both pro- and antitumourigenic properties have been attributed to NO.
  
  
  METHODS
  The expression of the inducible isoform of NO synthase (iNOS) was knocked down in the C6 glioma cell line using constitutive expression of antisense RNA, and the effect of tumour-derived NO on tumour progression and angiogenesis was investigated.
  
  
  RESULTS
  Tumours in which iNOS expression was decreased displayed significantly reduced growth rates compared with tumours derived from parental C6 cells. Quantitative non-invasive magnetic resonance imaging and fluorescence microscopy of tumour uptake of Hoechst 33342, and haematoxylin and eosin staining, revealed significantly impaired vascular development and function in antisense iNOS tumours compared with control in vivo, primarily associated with the more necrotic tumour core. Decreased iNOS expression had no effect on tumour VEGF expression.
  
  
  CONCLUSIONS
  Nitric oxide derived from tumour iNOS is an important modulator of tumour progression and angiogenesis in C6 gliomas and further supports the therapeutic strategy of inhibiting iNOS for the treatment of cancer.
authors.affiliation: Division of Basic Medical Sciences, St George's University of London, Cranmer Terrace, London SW17 ORE, UK.
authors.forename: V
authors.initials: V
authors.lastname: Kostourou
authors.forename: J E
authors.initials: JE
authors.lastname: Cartwright
authors.forename: A P
authors.initials: AP
authors.lastname: Johnstone
authors.forename: J K R
authors.initials: JK
authors.lastname: Boult
authors.forename: E R
authors.initials: ER
authors.lastname: Cullis
authors.forename: Gstj
authors.initials: G
authors.lastname: Whitley
authors.forename: S P
authors.initials: SP
authors.lastname: Robinson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000098:blood supply* / Q000201:enzymology* / Q000473:pathology; D016373:DNA, Antisense / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D020868:Gene Silencing / Q000502:physiology; D005910:Glioma / Q000098:blood supply* / Q000201:enzymology* / Q000473:pathology; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D051381:Rats; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D016373:DNA, Antisense; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat