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

Pancreas. 1999 Oct;19(3):281-8. doi: 10.1097/00006676-199910000-00009.


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- antisense transfected clones displayed markedly reduced glypican- 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 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Division / drug effects
  • DNA, Antisense / biosynthesis
  • DNA, Antisense / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression / drug effects
  • Growth Substances / genetics
  • Growth Substances / pharmacology
  • Heparan Sulfate Proteoglycans / biosynthesis
  • Heparan Sulfate Proteoglycans / genetics*
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Polysaccharide-Lyases / metabolism
  • RNA, Antisense / biosynthesis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / pharmacology
  • Transfection
  • Tumor Cells, Cultured


  • DNA, Antisense
  • Growth Substances
  • Heparan Sulfate Proteoglycans
  • RNA, Antisense
  • RNA, Messenger
  • Polysaccharide-Lyases
  • heparitinsulfate lyase