title: The impact of tumor nitric oxide production on VEGFA expression and tumor growth in a zebrafish rat glioma xenograft model.
abstract: To investigate the effect of nitric oxide on tumor development, we established a rat tumor xenograft model in zebrafish embryos. The injected tumor cells formed masses in which nitric oxide production could be detected by the use of the cell-permeant DAF-FM-DA (diaminofluorophore 4-amino-5-methylamino-2'-7'-difluorofluorescein diacetate) and DAR-4M-AM (diaminorhodamine-4M). This method revealed that nitric oxide production could be co-localized with the tumor xenograft in 46% of the embryos. In 85% of these embryos, tumors were vascularized and blood vessels were observed on day 4 post injection. Furthermore, we demonstrated by qRT-PCR that the transplanted glioma cells highly expressed Nos2, Vegfa and Cyclin D1 mRNA. In the xenografted embryos we also found increased zebrafish vegfa expression. Glioma and zebrafish derived Vegfa and tumor Cyclin D1 expression could be down regulated by the nitric oxide scavenger 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide or CPTIO. We conclude that even if there is a heterogeneous nitric oxide production by the xenografted glioma cells that impacts Vegfa and Cyclin D1 expression levels, our results suggest that reduction of nitric oxide levels by nitric oxide scavenging could be an efficient approach to treat glioma.
authors.affiliation: INSERM, UMR 866, 'Equipe Labellisée Ligue Contre le Cancer', Dijon, France; University of Burgundy, UFR SVTE, Dijon, France.
authors.forename: Nadhir
authors.initials: N
authors.lastname: Yousfi
authors.affiliation: University of Burgundy, UFR SVTE, Dijon, France.
authors.forename: Benoist
authors.initials: B
authors.lastname: Pruvot
authors.affiliation: INSERM, UMR 866, 'Equipe Labellisée Ligue Contre le Cancer', Dijon, France; University of Burgundy, UFR SVTE, Dijon, France.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Lopez
authors.affiliation: EA 7269, Ecole Pratique des Hautes Etudes, Dijon, France.
authors.forename: Lea
authors.initials: L
authors.lastname: Magadoux
authors.affiliation: EA 7269, Ecole Pratique des Hautes Etudes, Dijon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Franche
authors.affiliation: University of Burgundy, UFR SVTE, Dijon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pichon
authors.affiliation: University of Burgundy, UFR SVTE, Dijon, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Salvadori
authors.affiliation: INSERM U1009, Institut Gustave Roussy, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.affiliation: INSERM, UMR 866, 'Equipe Labellisée Ligue Contre le Cancer', Dijon, France.
authors.forename: Carmen
authors.initials: C
authors.lastname: Garrido
authors.affiliation: University of Burgundy, UFR SVTE, Dijon, France; EA 7269, Ecole Pratique des Hautes Etudes, Dijon, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Laurens
authors.affiliation: INSERM, UMR 866, 'Equipe Labellisée Ligue Contre le Cancer', Dijon, France; University of Burgundy, UFR SVTE, Dijon, France.
authors.forename: Johanna
authors.initials: J
authors.lastname: Chluba
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D019938:Cyclin D1 / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005910:Glioma / Q000378:metabolism*; D064593:Heterografts; D006652:Histological Techniques; D007093:Imidazoles / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D001565:Benzoates; D007093:Imidazoles; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D019938:Cyclin D1; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide