title: Expression of basic fibroblast growth factor is necessary but insufficient for production of metastasis.
abstract: 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-IO, 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 TV genes.
authors.affiliation: UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT CELL BIOL,HOUSTON,TX 77030.
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.forename: R
authors.initials: R
authors.lastname: Reich
authors.forename: R
authors.initials: R
authors.lastname: Radinsky
authors.forename: K
authors.initials: K
authors.lastname: Berry
authors.forename: B
authors.initials: B
authors.lastname: Dave
authors.forename: I
authors.initials: I
authors.lastname: Fidler