Open AccessInhibition of fibroblast growth factor receptor 2 attenuates proliferation and invasion of pancreatic cancer
Author(s) -
Matsuda Yoko,
Yoshimura Hisashi,
Suzuki Taeko,
Uchida Eiji,
Naito Zenya,
Ishiwata Toshiyuki
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12470
Subject(s) - fibroblast growth factor receptor , transfection , cancer research , pancreatic cancer , fibroblast growth factor , vascular endothelial growth factor , biology , cancer cell , cancer , microbiology and biotechnology , receptor , cell culture , medicine , biochemistry , genetics , vegf receptors
The alternative splicing of the extracellular domain of fibroblast growth factor receptor ( FGFR )‐2 generates the III b and III c isoforms. Expression of FGFR ‐2 III b correlates with vascular endothelial growth factor‐A ( VEGF ‐A) expression and venous invasion of pancreatic ductal adenocarcinoma ( PDAC ). By contrast, FGFR ‐2 III c expression correlates with faster development of liver metastasis after surgery, and increased proliferation rates and invasion of the cancer. In this study, we analyzed the expression and roles of total FGFR ‐2 (both isoforms) to determine the effectiveness of FGFR ‐2‐targeting therapy for PDAC . Immunohistochemically, FGFR ‐2 was highly expressed in 25/48 (52.1%) PDAC cases, and correlated with advanced stage cancer. In FISH analysis, FGFR 2 was amplified in 3/7 PDAC cell lines. We stably transfected an FGFR ‐2 sh RNA targeting the III b and III c isoforms into FGFR 2 ‐amplified PDAC cells. The proliferation rates, migration, and invasion of FGFR ‐2‐sh RNA ‐transfected cells were lower than those of control cells in vitro . In response to FGF ‐2, FGFR ‐2‐sh RNA ‐transfected cells showed decreased phosphorylation of ERK compared with control cells. The FGFR ‐2‐sh RNA ‐transfected cells also expressed lower levels of vascular endothelial growth factor‐A than control cells, and formed smaller s.c. tumors in nude mice. These findings suggest that FGFR ‐2 is a therapeutic target for inhibition in PDAC .