title: The zebrafish/tumor xenograft angiogenesis assay as a tool for screening anti-angiogenic miRNAs.
abstract: The zebrafish/tumor xenograft angiogenesis assay is used to approach tumor angiogenesis, a pivotal step in cancer progression and target for anti-tumor therapies. Here, we evaluated whether the assay could allow the identification of microRNAs having an anti-angiogenic potential. For that, we transfected DU-145 prostate cancer cells with four microRNAs (miR-125a, miR-320, miR-487b, miR-492) responsive to both anti- and pro-angiogenic stimuli applied to human umbilical vein endothelial cells. After transfection, DU-145 cells were injected close to the developing subintestinal vessels of transgenic Tg(Kdrl:eGFP)s843 zebrafish embryos that express green fluorescent protein under the control of Kdrl promoter. At 72 h post-fertilization, we observed that green fluorescent protein-positive neo-vessels infiltrated the graft of DU-145 transfected with miR-125a, miR-320, and miR-487b. Vice versa, neo-vessel formation and tumor cell infiltration were inhibited when DU-145 cells transfected with miR-492 were used. These results indicated that the zebrafish/tumor xenograft assay was adequate to identify microRNAs able to suppress the release of angiogenic growth factors by angiogenic tumor cells.
authors.affiliation: Institute of Clinical Physiology, Area della Ricerca CNR, Via Moruzzi, 156124, Pisa, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Chiavacci
authors.affiliation: Institute of Clinical Physiology, Area della Ricerca CNR, Via Moruzzi, 156124, Pisa, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Rizzo
authors.affiliation: Institute of Clinical Physiology, Area della Ricerca CNR, Via Moruzzi, 156124, Pisa, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Pitto
authors.affiliation: Institute of Clinical Physiology, Area della Ricerca CNR, Via Moruzzi, 156124, Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Patella
authors.affiliation: Institute of Clinical Physiology, Area della Ricerca CNR, Via Moruzzi, 156124, Pisa, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Evangelista
authors.affiliation: Institute of Clinical Physiology, Area della Ricerca CNR, Via Moruzzi, 156124, Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mariani
authors.affiliation: Institute of Clinical Physiology, Area della Ricerca CNR, Via Moruzzi, 156124, Pisa, Italy. g.rainaldi@ifc.cnr.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rainaldi
keywords: Prostate tumor cells; Tumor angiogenesis; Zebrafish/tumor xenografts; microRNAs