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

Kleeff J., WILDI S., Kumbasar A., FRIESS H., LANDER A., KORC M.

PANCREAS, vol.19, no.3, pp.281-288, 1999 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 19 Issue: 3
  • Publication Date: 1999
  • Doi Number: 10.1097/00006676-199910000-00009
  • Journal Name: PANCREAS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.281-288
  • Istanbul Technical University Affiliated: No


Glypican-1 belongs to a family of glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycans (HSPGs) that affect cell growth, invasion, and adhesion. Cell-surface HSPGs are believed to act as co-receptors for heparin-binding 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 heparin- binding growth factors that are commonly overexpressed in pancreatic cancer: fibroblast growth factor-2 (FGF2), heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), and hepatocyte growth factor (HGF). In addition, glypican-1 antisense-expressing, a 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.