Antiangiogenic properties of fibstatin, an extracellular FGF-2-binding polypeptide.
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.
Bossard
Carine
C
Institut National de la Santé et de la Recherche Médicale (INSERM) U589, C.H.U. Rangueil, Toulouse, France.
Van den Berghe
Loic
L
Laurell
Henrik
H
Castano
Caroline
C
Cerutti
Martine
M
Prats
Anne-Catherine
AC
Prats
Hervé
H
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018076:DNA, Complementary / Q000008:administration & dosage / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D008546:Melanoma, Experimental / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology
D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D011994:Recombinant Proteins; C493535:fibstatin protein, human; D016222:Fibroblast Growth Factor 2