Stable Transfection of a Glypican-1 Antisense Construct Decreases Tumorigenicity in PANC-1 Pancreatic Carcinoma Cells

Abstract

Summary

Glypican-1 belongs to a family of glycosylphosphatidylinositol (GP1)-anchored heparan sulfate proteoglycans (HSPGs) that affect cell growth, invasion, and adhesion. Cellsurface HSPGs are believed to act as co-receptors for heparinbinding mitogenic growth factors. It was reported that glypican-1 is strongly expressed in human pancreatic cancer, and that it may play an essential role in regulating growth-factor responsiveness in pancreatic carcinoma 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 were stable transfected with a full-length glypican- 1 antisense construct. The glypican- 1 antisense transfected clones displayed markedly reduced glypican- 1 protein levels and a marked attenuation of the mitogenic responses to heparinbinding growth factors that are commonly overexpressed in pancreatic cancer: fibroblast growth factor-2 (FGF2), heparinbinding epidermal growth factor (EGF)-like growth factor(HB-EGF), and hepatocyte growth factor (HGF). In addition, glypican-1 antisense-expressing PANC- 1 cells exhibited a significantly reduced ability to form tumors in nude mice in comparison with parental and sham-transfected PANC- 1 cells. These data suggest that glypican-1 plays an important role in the responses of pancreatic cancer cells to heparin-binding growth factors, and documents for the first time that its expression may enhance tumorigenic potential in vivo.