EXPRESSION OF BASIC FIBROBLAST GROWTH-FACTOR IS NECESSARY BUT INSUFFICIENT FOR PRODUCTION OF METASTASIS

We determined whether overexpression of basic fibroblast growth factor (bFGF) is necessary for enhanced growth and production of metastasis by murine K-1735 melanoma cells. The bFGF gene was transfected into th ree nonmetastatic clones (C-IO, C-19, and C-23) that do not express bF GF mRNA and protein and one metastatic clone that expresses high level s of bFGF mRNA and protein. Control cells were transfected with a domi nant selectable marker neomycin resistance gene (neo). All bFGF-transd uced cells expressed bFGF-specific mRNA transcripts and cellular bFGF protein and proliferated in culture with medium containing low concent rations of serum. Anchorage-independent growth in hard agarose was enh anced only in bFGF-transfected nonmetastatic C-10 cells which, subsequ ent to the transfection, also expressed high levels of collagenase IV/ gelatinase A activity. The treatment of C-10, C-19, and C-23 cells wit h exogenous bFGF induced collagenase IV/gelatinase expression, as did the addition of lysates from C-10/bFGF and C-23/bFGF cells. C-10/bFGF cells (but not C-19/bFGF or C-23/bFGF) produced highly vascular and ra pidly growing subcutaneous tumors as well as a high incidence of lung metastasis. These data suggest that overexpression of bFGF is necessar y but in itself not sufficient to convert nonmetastatic K-1735 cells t o the metastatic phenotype and that enhanced tumorigenicity and metast asis require at least concurrent expression of bFGF and collagenase ty pe TV genes.