Basic fibroblast growth factor regulates matrix metalloproteinases production and in vitro invasiveness in human bladder cancer cell lines

Purpose: This study was designed to investigate the effect of endogenous basic fibroblast growth factor (FGF-2) on matrix metalloproteinases (MMPs) production and in vitro invasive potential of human bladder cancer cell lines. Materials and Methods: The human bladder cancer cell lines, HT1376 and KoTCC-1, were used in this study. The mRNA for FGF receptor has been shown to be expressed in both cell lines; the mRNA for FGF-2 is expressed in only KoTCC-1. The effects of FGF-2 expression on HT1376 by gene transfection and those of FGF-2 antisense oligonucleotides treatment on KoTCC-1 were analyzed by zymography and in vitro tumor cell invasion assay. Results: The introduction of human FGF-2 gene into HT1376 cells markedly enhanced both the MMP-2 and MMP-9 production, and the in vitro invasive potential was also increased. In contrast, the exposure of KoTCC-1 cells to FGF-2 specific antisense oligonucleotides decreased the MMP-2 production and in vitro invasive potential, but the exposure to FGF-2 sense oligonucleotides did not. Conclusions: These findings suggest that FGF-S plays an important role in the invasive process of human bladder cancer in part through the regulation of MMPs production.