Stable transfection of a glypican-1 antisense construct decreases tumorigenicity in PANC-1 pancreatic carcinoma cells

Glypican-1 belongs to a family of glycosylphosphatidylinositol (GPI)-anchor ed heparan sulfate proteoglycans (HSPGs) that affect cell growth, invasion, and adhesion. Cell-surface HSPGs are believed to act as co-receptors for h eparin-binding mitogenic growth factors. It was reported that glypican-1 is strongly expressed in human pancreatic cancer, and that it may play an ess ential role in regulating growth-factor responsiveness in pancreatic carcin oma cells. In this study we investigated the effects of decreased glypican- 1 expression in PANC-1 pancreatic cancer cells. To this end, PANC-1 cells w ere stable transfected with a full-length glypican-1 antisense construct. T he glypican-1 antisense transfected clones displayed markedly reduced glypi can-1 protein levels and a marked attenuation of the mitogenic responses to heparin- binding growth factors that are commonly overexpressed in pancrea tic cancer: fibroblast growth factor-2 (FGF2), heparin-binding epidermal gr owth factor (EGF)-like growth factor (HB-EGF), and hepatocyte growth factor (HGF). In addition, glypican-1 antisense-expressing, a PANC-1 cells exhibi ted a significantly reduced ability to form tumors in nude mice in comparis on with parental and sham-transfected PANC-1 cells. These data suggest that glypican-1 plays an important role in the responses of pancreatic cancer c ells to heparin-binding growth factors, and documents for the first time th at its expression may enhance tumorigenic potential in vivo.