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

Jörg Kleeff, Stefan Wildi, Asli Kumbasar, Helmut Friess, Arthur D. Lander, Murray Korc

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)281-288
Number of pages8
JournalPancreas
Volume19
Issue number3
DOIs
StatePublished - Oct 1999

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Keywords

  • Antisense
  • Glypican-1
  • Growth factors
  • Heparin-binding
  • Pancreatic cancer

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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