Alterations of blood vessel development by endothelial cells overexpressing fibroblast growth factor-2

A close relationship exists between angiogenesis and the formation of vascu lar lesions, The development of the vascular system in the chick embryo cho rioallantoic membrane (CAM) may thus represent a model to study the effects of the deregulation of endothelial cell behaviour, Alterations of the deve loping vascular tree of the CAM were observed after exposure to murine aort ic endothelial (MAE) cells overexpressing human fibroblast growth factor-2 (FGF2) cDNA (pZipFGF2 MAE cells), or to their conditioned medium (CM), pZip FGF2 MAE cells injected into the allantoic sac or applied on to the CAM of day 8-9 chick embryos induce neovascularization and the appearance of haema ngioma-like lesions. This activity was not prevented by anti-FGF2 antibodie s, The CM from pZipFGF2 MAE cells was also active when adsorbed into a gela tin sponge and applied on to the CAM, both in the absence and in the presen ce of anti-FGF2 antibodies. No effects on vessel development mere exerted b y parental MAE cells, FGF2-transfected NIH 3T3 fibroblasts, or their condit ioned media, In vitro, pZipFGF2 MAE cell CM caused parental MAE cells to in vade fibrin gels and to undergo morphogenesis on Matrigel. This activity wa s not mimicked by recombinant FGF2 nor affected by anti-FGF2 antibodies, an d depended on a M-r similar to 45 000 heat-labile heparin-binding factor. S ize exclusion chromatography of pZipFGF2 MAE cell CM demonstrated that the in vitro activity co-purified with an in vivo angiogenic capacity, Thus, FG F2 overexpression in mouse endothelial cells induces the production of an a ngiogenic activity distinct from FGF2, which may contribute to the genesis of angioproliferative lesions, Copyright (C) 1999 John Wiley & Sons, Ltd.