ABSTRACT

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 isoform of FGF receptor-2 (FGFR2) and the novel glycosaminoglycan-modified FGFR2/IIIc/Ig-2 loops isoform. 

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 an increased proliferative capacity, more evident for FGF2 than FGF4 transfectants (pZipFGF2-MAE and pZipFGF4-MAE cells, respectively). 

Both cell types induce angiogenesis when applied on the top the of chick embryo chorioallantoic membrane. However, in contrast with FGF2-transfected cells, pZipFGF4-MAE cells lack the ability to invade 3D fibrin gel and to undergo morphogenesis in vitro and 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. 
 

Oncogene (2001) 20: 2655-2663