GROWTH ADVANTAGE AND VASCULARIZATION INDUCED BY BASIC FIBROBLAST GROWTH-FACTOR OVEREXPRESSION IN ENDOMETRIAL HEC-1-B CELLS - AN EXPORT-DEPENDENT MECHANISM OF ACTION

The human endometrial adenocarcinoma HEC-1-B cell line was transfected with an expression vector harboring the human basic fibroblast growth factor (bFGF) cDNA under the control of the human beta-actin gene pro moter. Stable transfectants were obtained in which a constitutive, lim ited overexpression of M(r) 24,000, 22,000, and 18,000 bFGF isoforms w as observed. When transfectants were screened for the capacity to rele ase the growth factor, significant amounts of bFGF were present in the conditioned medium and extracellular matrix of the bPGF-B9 clone but not of the bFGF-AB clone, even though both cell lines produced similar levels of intracellular bFGF. When compared to parental cells, bFGF-B 9 cells showed down-regulation of tyrosine kinase fibroblast growth fa ctor receptors along with up-regulation of urokinase-type plasminogen activator expression which was abolished by incubation of the cell cul tures with neutralizing anti-bFGF antibody. In vivo, bFGF-B9 cells for med highly vascularized tumors growing faster than parental cells when injected s.c. in nude mice. Also, they were more potent than nontrans fected cells in inducing an angiogenic response in the rabbit cornea a ssay. In contrast, the bFGF-A8 cell phenotype was indistinguishable fr om parental cells both in vitro and in vivo. In conclusion, clonal dif ferences exist within the HEC-1-B cell line in the capacity to release bFGF. bFGF export by human endometrial adenocarcinoma cells results i n autocrine and paracrine effects that confer a growth advantage in vi vo associated with increased neovascularization.