Vascular leakage in chick embryos after expression of a secreted binding protein for fibroblast growth factors

Fibroblast growth factors (FGFs) have been implicated in a variety of physiologic and pathologic processes from embryonic development to tumor growth and angiogenesis. FGFs are immobilized in the extracellular matrix of different tissues and require release from this storage site to trigger a respon...

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Bibliographic Details
Published in:Laboratory investigation 2005-06, Vol.85 (6), p.747-755
Main Authors: MCDONNELL, Kevin, BOWDEN, Emma T, CABAL-MANZANO, Rafael, HOXTER, Becky, RIEGEL, Anna T, WELLSTEIN, Anton
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biotechnology
Chick Embryo
Fibroblast Growth Factors - genetics
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Genes, Reporter
Green Fluorescent Proteins - genetics
Humans
Investigative techniques, diagnostic techniques (general aspects)
Kinetics
Medical sciences
Neoplasms - blood supply
Neovascularization, Pathologic - pathology
Neovascularization, Physiologic - physiology
Receptors, Fibroblast Growth Factor - genetics
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Summary:Fibroblast growth factors (FGFs) have been implicated in a variety of physiologic and pathologic processes from embryonic development to tumor growth and angiogenesis. FGFs are immobilized in the extracellular matrix of different tissues and require release from this storage site to trigger a response. Secreted FGF-binding proteins (FGF-BPs) can release immobilized FGFs, enhance the activity of locally stored FGFs and can thus serve as an angiogenic switch molecule in cancer. Here, we report on the effect of human FGF-BP transgene expression in chicken embryos. To establish the transgenic model, plasmid-based reporter vectors expressing luciferase, beta-galactosidase or green fluorescent protein were introduced through different routes into 4- to 5-day-old embryos grown outside their egg shell on top of the yolk sac. This allows for easy manipulation and continuous observation of phenotypic effects. Expression of human FGF-BP induced dose-dependent vascular permeability, hemorrhage and embryonic lethality. Light and electron microscopic studies indicate that this hemorrhage results from compromised microvascular structure. An FGF-1 expression vector with an added secretory signal mimicked this vascular leakiness phenotype whereas wild-type FGF-1 required coexpression of a threshold amount of FGF-BP. This model is a powerful tool for real-time monitoring of the effects of transient transgene expression during embryogenesis.
ISSN:0023-6837
1530-0307
DOI:10.1038/labinvest.3700269