The 18 kDa isoform of basic fibroblast growth factor is sufficient to stimulate human melanoma growth and angiogenesis

Basic fibroblast growth factor is the best-characterized autocrine growth factor in melanoma development and progression. We hypothesized that basic fibroblast growth factor might induce a more aggressive phenotype dependent on the amount of protein expressed in melanoma. Two human melanoma cell lines, M14 and 1F6, known to have low endogenous basic fibroblast growth factor expression and slow growth as subcutaneous xenografts, were stably transfected with vectors encoding either the 18 kDa or all (ALL) isoform proteins of human basic fibroblast growth factor. Different clones overexpressing the 18 kDa or ALL basic fibroblast growth factor proteins were easily obtained. Increased levels of basic fibroblast growth factor were secreted in conditioned medium and stored on the extracellular membrane. Biological activity of the overexpressed basic fibroblast growth factor was confirmed in a human umbilical vein endothelial cell proliferation assay. In 1F6 cells, overexpression of either 18 kDa or ALL basic fibroblast growth factor proteins resulted in up to two-fold shorter in-vitro doubling times (P<0.05). In addition, in vivo, both 18 kDa and ALL basic fibroblast growth factor-overexpressing 1F6 subcutaneous xenografts displayed significantly higher growth rates (P