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

Toshiyuki Ishiwata, Yoko Matsuda, Tetsushi Yamamoto, Eiji Uchida, Murray Korc, Zenya Naito

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1928-1941
Number of pages14
JournalAmerican Journal of Pathology
Volume180
Issue number5
DOIs
StatePublished - May 2012

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Receptor, Fibroblast Growth Factor, Type 2
Pancreatic Neoplasms
Cell Proliferation
Adenocarcinoma
Receptor, Fibroblast Growth Factor, Type 1
Neoplasms
Protein Isoforms
Side-Population Cells
Neoplasm Metastasis
Neoplastic Stem Cells
Liver
Extracellular Signal-Regulated MAP Kinases
Fibroblast Growth Factor 2
Cell Movement

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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Enhanced expression of fibroblast growth factor receptor 2 IIIc promotes human pancreatic cancer cell proliferation. / Ishiwata, Toshiyuki; Matsuda, Yoko; Yamamoto, Tetsushi; Uchida, Eiji; Korc, Murray; Naito, Zenya.

In: American Journal of Pathology, Vol. 180, No. 5, 05.2012, p. 1928-1941.

Research output: Contribution to journalArticle

Ishiwata, Toshiyuki ; Matsuda, Yoko ; Yamamoto, Tetsushi ; Uchida, Eiji ; Korc, Murray ; Naito, Zenya. / Enhanced expression of fibroblast growth factor receptor 2 IIIc promotes human pancreatic cancer cell proliferation. In: American Journal of Pathology. 2012 ; Vol. 180, No. 5. pp. 1928-1941.
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