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 three nonmetastatic clones (C-10, C-19, and C-23) that do not express bFGF mRNA and protein and one metastatic clone that expresses high levels of bFGF mRNA and protein. Control cells were transfected with a dominant selectable marker neomycin resistance gene (neo). All bFGF-transduced cells expressed bFGF-specific mRNA transcripts and cellular bFGF protein and proliferated in culture with medium containing low concentrations of serum. Anchorage-independent growth in hard agarose was enhanced only in bFGF-transfected nonmetastatic C-10 cells which, subsequent to the transfection, also expressed high levels of collagenase IV/gelatinase A activity. The treatment of C-10, C-19, and C-23 cells with 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 rapidly growing subcutaneous tumors as well as a high incidence of lung metastasis. These data suggest that overexpression of bFGF is necessary but in itself not sufficient to convert nonmetastatic K-1735 cells to the metastatic phenotype and that enhanced tumorigenicity and metastasis require at least concurrent expression of bFGF and collagenase type IV genes.