Enhanced expression of fibroblast growth factor receptor 2 IIIc promotes human pancreatic cancer cell proliferation

Am J Pathol. 2012 May;180(5):1928-41. doi: 10.1016/j.ajpath.2012.01.020. Epub 2012 Mar 19.


In pancreatic ductal adenocarcinoma (PDAC), the fibroblast growth factor receptor 1 (FGFR-1) IIIb isoform correlates with the inhibition of cancer cell proliferation, migration, and invasion, whereas FGFR-1 IIIc enhances cancer cell proliferation. The FGFR-2 IIIb isoform is expressed in PDAC, and its expression correlates with increased venous invasion. We examined the role of FGFR-2 IIIc in PDAC. FGFR-2 IIIc was expressed in all six pancreatic cancer cell lines examined and was highest in PANC-1 cells. FGFR-2 IIIc was abundant in the cancer cells from 83 of 117 PDAC cases, which correlated with decreased duration to development of liver metastasis after surgery. FGFR-2 IIIc-transfected cells exhibited increased proliferation in vitro and formed larger subcutaneous and orthotopic tumors, the latter producing more liver metastases. Moreover, FGF-2 exerted a more rapid stimulatory effect on the levels of phosphorylated extracellular signal-regulated kinase (p-ERK) in FGFR-2 IIIc stably transfected PANC-1 cells, compared with control cells. FGFR-2 IIIc-transfected cells also formed more spheres and contained more side population cells. Suppression of FGFR-2 IIIc expression inhibited the proliferation of PANC-1 cells, whereas an anti-FGFR-2 IIIc antibody inhibited the proliferation and migration of PANC-1 cells. Thus, high FGFR-2 IIIc levels in PDAC contribute to disease aggressiveness and confer to pancreatic cancer cells features suggestive of cancer stem cells, indicating that FGFR-2 IIIc may be a novel and important therapeutic target in PDAC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / secondary
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Real-Time Polymerase Chain Reaction / methods
  • Receptor, Fibroblast Growth Factor, Type 2 / biosynthesis*
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics
  • Receptor, Fibroblast Growth Factor, Type 2 / physiology
  • Transfection
  • Transplantation, Heterologous


  • Neoplasm Proteins
  • Protein Isoforms
  • RNA, Messenger
  • RNA, Neoplasm
  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2