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Expression and differential regulation of connective tissue growth factor in pancreatic cancer cells

C Wenger1, V Ellenrieder, B Alber

  • 1Department of Internal Medicine I, University of Ulm, Germany.

Oncogene
|February 19, 1999
PubMed

Insights

Connective tissue growth factor (CTGF) is upregulated in pancreatic cancer, promoting the desmoplastic reaction. Fibroblasts, not tumor cells, are the primary source of CTGF in these tissues.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Connective tissue growth factor (CTGF) acts as a downstream mediator of transforming growth factor-beta (TGFbeta) in fibroblasts and vascular endothelial cells.
  • CTGF is an immediate early growth responsive gene, indicating its rapid induction by growth factors.

Purpose of the Study:

  • To investigate the role of CTGF as an immediate early target gene of epidermal growth factor (EGF)/transforming growth factor-alpha (TGFalpha) in human pancreatic cancer cells.
  • To determine the expression levels and correlation of CTGF with fibrosis in pancreatic cancer tissues and xenografts.

Main Methods:

  • Suppression hybridization was used to isolate hCTGF as a target gene.
  • Quantitative analysis of CTGF transcript levels in pancreatic cancer cell lines and tissues using techniques like in situ hybridization.
  • Nude mouse xenograft models were employed to study CTGF expression and its relation to fibrosis in vivo.

Main Results:

  • CTGF transcripts were detected in a majority of pancreatic cancer cell lines and human tissues, with significant overexpression in 15/19 tissues.
  • EGF/TGFalpha induced CTGF transcript levels in some cell lines, while TGFbeta also increased CTGF levels, sustained over 24 hours.
  • CTGF transcript levels correlated positively with the degree of fibrosis in pancreatic cancer tissues and xenograft tumors, with fibroblasts being the main source.

Conclusions:

  • CTGF is significantly overexpressed in human pancreatic cancer and is induced by growth factors like EGF, TGFalpha, and TGFbeta.
  • The expression of CTGF in pancreatic cancer tissues is strongly associated with the desmoplastic reaction and fibrosis.
  • Fibroblasts are identified as the predominant cells transcribing CTGF in pancreatic cancer, suggesting CTGF's critical role in desmoplasia.

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