Abstract
By using the two-hybrid system with basic fibroblast growth factor (FGF-2) as bait, we isolated and characterized fibstatin, an endogenous M(r) 29,000 human basement membrane-derived inhibitor of angiogenesis and tumor growth. Fibstatin, a fragment containing the type III domains 12-14 of fibronectin, was produced as a recombinant protein and was shown to inhibit the proliferation, migration, and differentiation of endothelial cells in vitro. Antiangiogenic activity of fibstatin was confirmed in a Matrigel angiogenesis assay in vivo, and electrotransfer of the fibstatin gene into muscle tissue resulted in reduced B16F10 tumor growth. Taken together, these results suggest that fibstatin could act as a powerful molecule for antiangiogenic therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / isolation & purification
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Carrier Proteins / metabolism
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Carrier Proteins / pharmacology*
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Cell Division / drug effects
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Cell Movement / drug effects
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DNA, Complementary / administration & dosage
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DNA, Complementary / genetics
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Female
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Fibroblast Growth Factor 2 / metabolism*
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Gene Transfer Techniques
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HeLa Cells
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Humans
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Melanoma, Experimental / blood supply
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Melanoma, Experimental / genetics
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Melanoma, Experimental / pathology
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Membrane Proteins / genetics
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Membrane Proteins / isolation & purification
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Membrane Proteins / metabolism
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Membrane Proteins / pharmacology*
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Mice
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Mice, Inbred C57BL
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NIH 3T3 Cells
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Neovascularization, Pathologic / drug therapy
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Recombinant Proteins / genetics
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacology
Substances
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Carrier Proteins
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DNA, Complementary
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Membrane Proteins
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Recombinant Proteins
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fibstatin protein, human
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Fibroblast Growth Factor 2