Insulin-like growth factor II activates mitogenic signaling in pancreatic cancer cells via IRS-1: In vivo evidence for an islet-cancer cell axis

Uwe Bergmann, Hitoshi Funatomi, Marko Kornmann, Toshiyuki Ishiwata, Hans G. Beger, Murray Korc

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Insulin-like growth factor-II (IGF-II) action and expression were examined in 3 human pancreatic cancer cell lines. IGF-II expression was also studied in 17 normal and 12 malignant pancreatic tissues. IGF-II enhanced the growth of all 3 cell lines. In COLO-357 and PANC-1 cells, one-half maximal stimulation occurred at 0.3 and 0.4 nM IGF-II, respectively. In ASPC-1 cells, one-half maximal stimulation occurred at 0.9 nM IGF-II. A monoclonal antibody (cdR3) that blocks ligand binding to the insulin-like growth factor I (IGF-I) receptor (IGF-IR) inhibited IGF-II-mediated growth stimulation, and IGF-II enhanced insulin-receptor substrate 1 (IRS-1) phosphorylation. IGF-II mRNA transcripts were present in COLO-357 cells, in 4 of 17 normal human pancreatic tissues, and in 8 of the 12 cancer samples. By immunohistochemistry, IGF-II was present in the islets of both normal and malignant pancreatic tissues, and occasionally in the cancer cells within the tumor mass. These findings indicate that IGF-II acts via IGF-IR to enhance mitogenic signaling in pancreatic cancer cells and suggest that islet-derived IGF-II may contribute to pancreatic cancer cell growth in vivo.

Original languageEnglish (US)
Pages (from-to)487-492
Number of pages6
JournalInternational journal of oncology
Volume9
Issue number3
StatePublished - Sep 1 1996

Keywords

  • IGF-I
  • IGF-II
  • IRS-1
  • pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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