Vascular endothelial growth factor overproduced by tumour cells acts predominantly as a potent angiogenic factor contributing to malignant progression

To elucidate the role of vascular endothelial growth factor (VEGF), an endo thelial cell-specific mitogen, in tumour angiogenesis and malignant progres sion, an expression vector harboring human VEGF cDNA was stably transfected into three human cancer cell lines with poor VEGF productivity. Though the ir in vitro growth rate and intrinsic productivity of another angiogenic fa ctor, basic fibroblast growth factor (bFGF), were not changed by transfecti on, those clones with higher VEGF production were endowed with tumorigenic and angiogenic potentials as follows: firstly, nontumorigenic, lung carcino ma QG90 cells having lower bFGF productivity acquired tumorigenicity as wel l as significant in vivo angiogenesis-inducing ability, secondly, tumorigen ic colorectal carcinoma RPM14788 cells having higher potency for bFGF produ ction could form more vascularized solid tumour with faster growth rate and thirdly, oestrogen-dependent breast carcinoma MCF-7 cells, which did not p roduce detectable bFGF, acquired tumorigenicity even in the absence of oest rogen and the solid tumour growth rate was remarkably enhanced, accompanied with increased vascularization, in the presence of oestrogen. These result s suggest that tumour progression closely depends on angiogenesis, and VEGF significantly contributes to malignant progression of a variety of tumour cells through its potent angiogenic activity, independent on the bFGF produ ctivity of tumour cells.