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 Citations (Scopus)

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
StatePublished - Oct 1999
Externally publishedYes

Fingerprint

Glypicans
Transfection
Pancreatic Neoplasms
Intercellular Signaling Peptides and Proteins
Heparin
Heparan Sulfate Proteoglycans
Epidermal Growth Factor
Fibroblast Growth Factor Receptors
Glycosylphosphatidylinositols
Hepatocyte Growth Factor
Pancreatic Carcinoma
Fibroblast Growth Factor 2
Nude Mice
Clone Cells

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology

Cite this

Kleeff, J., Wildi, S., Kumbasar, A., Friess, H., Lander, A. D., & Korc, M. (1999). Stable transfection of a glypican-1 antisense construct decreases tumorigenicity in PANC-1 pancreatic carcinoma cells. Pancreas, 19(3), 281-288.

Stable transfection of a glypican-1 antisense construct decreases tumorigenicity in PANC-1 pancreatic carcinoma cells. / Kleeff, Jörg; Wildi, Stefan; Kumbasar, Asli; Friess, Helmut; Lander, Arthur D.; Korc, Murray.

In: Pancreas, Vol. 19, No. 3, 10.1999, p. 281-288.

Research output: Contribution to journalArticle

Kleeff, J, Wildi, S, Kumbasar, A, Friess, H, Lander, AD & Korc, M 1999, 'Stable transfection of a glypican-1 antisense construct decreases tumorigenicity in PANC-1 pancreatic carcinoma cells', Pancreas, vol. 19, no. 3, pp. 281-288.
Kleeff J, Wildi S, Kumbasar A, Friess H, Lander AD, Korc M. Stable transfection of a glypican-1 antisense construct decreases tumorigenicity in PANC-1 pancreatic carcinoma cells. Pancreas. 1999 Oct;19(3):281-288.
Kleeff, Jörg ; Wildi, Stefan ; Kumbasar, Asli ; Friess, Helmut ; Lander, Arthur D. ; Korc, Murray. / Stable transfection of a glypican-1 antisense construct decreases tumorigenicity in PANC-1 pancreatic carcinoma cells. In: Pancreas. 1999 ; Vol. 19, No. 3. pp. 281-288.
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