Antiangiogenic,antimigratory and antiinflammatory effects of 2-methoxyestradiol in zebrafish larvae |
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Authors: | Marisol Quezada Marjorie Alvarez Oscar A Peña Soledad Henríquez Claudia A d' Alençon Soledad Lange Barbara Oliva Gareth I Owen Miguel L Allende |
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Institution: | 1. Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile;2. FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Santiago, Chile;3. Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello, Santiago, Chile;4. Biomedical Research Consortium Chile (BMRC), Alameda 440, Piso 13, Santiago, Chile |
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Abstract: | 2-Methoxyestradiol (2ME), an endogenous metabolite of 17β-estradiol, has been previously reported to possess antiangiogenic and antitumor properties. Herein, we demonstrate that the effects of this antiangiogenic steroid can be readily assayed in live zebrafish, introducing a convenient and robust new model system as a screening tool for both single cell and collective cell migration assays. Using the in vitro mammalian endothelial cell line EA.hy926, we first show that cell migration and angiogenesis, as estimated by wound assay and tube formation respectively, are antagonized by 2ME. In zebrafish (Danio rerio) larvae, dose-dependent exposure to 2ME diminishes (1) larval angiogenesis, (2) leukocyte recruitment to damaged lateral line neuromasts and (3) retards the lateral line primordium in its migration along the body. Our results indicate that 2ME has an effect on collective cell migration in vivo as well as previously reported anti-tumorigenic activity and suggests that the molecular mechanisms governing cell migration in a variety of contexts are conserved between fish and mammals. Moreover, we exemplify the versatility of the zebrafish larvae for testing diverse physiological processes and screening for antiangiogenic and antimigratory drugs in vivo. |
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Keywords: | GFP green fluorescent protein 2ME 2-methoxyestradiol ISVs intersegmental vessels DLAV dorsal anastomotic vessels PAV parachordal anastomotic vessels |
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