Paracrine and autocrine effects of fibroblast growth factor-4 in endothelial cells.
Recombinant Fibroblast Growth Factor-4 (FGF4) and FGF2 induce extracellular signal-regulated kinase-1/2 activation and DNA synthesis in murine aortic endothelial (MAE) cells. These cells co-express the IIIc/Ig-3 loops and the novel glycosaminoglycan-modified IIIc/Ig-2 loops isoforms of FGF receptor-2 (FGFR2). The affinity of FGF4/FGFR2 interaction is 20-30 times lower than that of FGF2 and is enhanced by heparin. Overexpression of FGF2 or FGF4 cDNA in MAE cells results in a transformed phenotype and increased proliferative capacity, more evident for FGF2 than FGF4 transfectants. Both transfectants induce angiogenesis when applied on the top of the chick embryo chorioallantoic membrane. However, in contrast with FGF2-transfected cells, FGF4 transfectants show a limited capacity to growth under anchorage-independent conditions and lack the ability to invade 3D fibrin gel and to undergo morphogenesis in vitro. Also, they fail to induce hemangiomas when injected into the allantoic sac of the chick embryo. In conclusion, although exogenous FGF2 and FGF4 exert a similar response in MAE cells, significant differences are observed in the biological behavior of FGF4 versus FGF2 transfectants, indicating that the expression of the various members of the FGF family can differently affect the behavior of endothelial cells and, possibly, of other cell types, including tumor cells.
Dell'Era
P
P
Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, 25123 Brescia, Italy.
Belleri
M
M
Stabile
H
H
Massardi
M L
ML
Ribatti
D
D
Presta
M
M
D016475:3T3 Cells / Q000502:physiology; D000482:Allantois / Q000098:blood supply; D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection
C496445:FGF4 protein, human; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors