PLATzeb

Localization
INSERM U 1020, Université Bordeaux Bat. B2 Ouest
DEMANDE D'UTILISATION

Contact

Description

Zebrafish model for angiogenesis and tumorigenesis:  Zebrafish model has become widely used because of its fecundity, its morphological and physiological similarities to mammals, the existence of many genomic tools and the ease with which large, phenotype-based screens can be performed. In addition, a great advantage of the zebrafish model resides in its regeneration capacities allowing caudal fin regeneration after amputation even at the adult stage. It is therefore possible to study the effect of vaious drugs and the role of various genes in the regeneration process that requires cell proliferation, migration and adhesion, processes required for tumor progression and angiogenesis. The development of blood vessels in zebrafish embryos is well characterized and can be easily monitored (embryos have been used to show that tyrosine kinase inhibitors can prevent angiogenesis as measured with microangiography or endogenous alkaline phosphatase staining of blood vessels). Transgenic zebrafish lines with fluorescent (eGFP-labelled, transgenic fli-1) blood vessels have been developed, which greatly simplify the imaging of vessels.Usefulness of the zebrafish assay has been previously validated since observing phenotypic changes in whole animals exposed to small molecules has discovered numerous drugs.

Activity

Direct in vivo evaluation of the effect of genes expression and repression and coumpounds or drugs

Infrastructure and equipment

Zebrafish facilities for regenerative angiogenesis and oncogenesis studies

Publication

  1. Khatib AM, Lahlil R, Hagedorn M, Delomenie C, Christophe O, Denis C, Siegfried G. Biological outcome and mapping of total factor cascades in response to HIF induction during zebrafish regenerative angiogenesis. Oncotarget (submitted)
  2. Sfaxi F, Scamuffa N, Lalou C, Ma J, Metrakos P, Siegfried G, Ragg H, Bikfalvi A, Calvo F, Khatib AM. Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases. Oncotarget. 2014 Jun 30;5(12):4195-210.
  3. Scamuffa N, Sfaxi F, Ma J, Lalou C, Seidah N, Calvo F, Khatib AM. Prodomain of the proprotein convertase subtilisin/kexin Furin (ppFurin) protects from tumor progression and metastasis. Carcinogenesis. 2014 Mar;35(3):528-36. 4. Lalou C, Basak A, Mishra P, Mohanta BC, Banik R, Dinda B, Khatib AM. Inhibition of tumor cells proliferation and migration by the flavonoid furin inhibitor isolated from Oroxylum indicum. Curr Med Chem. 2013;20(4):583-91.
  4. Khatib AM, Lahlil R, Scamuffa N, Akimenko MA, Ernest S, Lomri A, Lalou C, Seidah NG, Villoutreix BO, Calvo F, Siegfried Zebrafish ProVEGF-C expression, proteolytic processing and inhibitory effect of unprocessed ProVEGF-C during fin regeneration. PLoS One. 2010 Jul 2;5(7):e11438.

Collaboration

  • Akimenko Marie-André. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada. Process of regeneration and angiogenesis in zebrafish.
  • Bruno Vitoutreix (Inserm. U648, Paris 5). Convertase-based drugs development using bioinformatic tools (Virtual ligand screening and protein-protein interactions) and their validation using the zebrafish facilities.
  • Stefan Kunz (University Hospital Center and University of Lausanne, Lausanne), development of SKI-1 inhibitors.
  • Nabil Seidah (IRCM, Montreal, Canada) identification of new convertases substrates and assess of the importance of their processing by the convertases in cancer.
  • Ajoy Basak (University of Ottawa, Ottawa, Canada) development of peptide-based anti-cancer compounds.