Human Fibroblast Growth Factor Receptor 1-IIIb Is a Functional Fibroblast Growth Factor Receptor Expressed in the Pancreas and Involved in Proliferation and Movement of Pancreatic Ductal Cells

Liu, Zhanbing; Ishiwata, Toshiyuki; Zhou, Shaxia; Maier, Susanne; Henne‐Bruns, Doris; Korc, Murray; Bachem, Max G.; Kornmann, Marko

doi:10.1097/mpa.0b013e318053e7e3

Cited by 9 publications

(9 citation statements)

References 19 publications

(41 reference statements)

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“…To assess the effect of kinase, inhibitors cells were incubated in the absence or presence of the p38-mitogen-activated protein kinase (MAPK) inhibitor SB203580 (Calbiochem, Darmstadt, Germany) and the cJun N-terminal kinase (JNK) inhibitor SP600125 (Calbiochem) for 24 h (Liu et al, 2007a).…”

Section: Anchorage-dependent Growth and Functional Assaysmentioning

confidence: 99%

“…To analyse N-linked protein, glycosylation cells were incubated in the absence or presence of tunicamycin (5 mg ml -1 , T7765 Sigma) for 24 h as described (Liu et al, 2007a). To assess the effect of kinase, inhibitors cells were incubated in the absence or presence of the p38-mitogen-activated protein kinase (MAPK) inhibitor SB203580 (Calbiochem, Darmstadt, Germany) and the cJun N-terminal kinase (JNK) inhibitor SP600125 (Calbiochem) for 24 h (Liu et al, 2007a).…”

Section: Anchorage-dependent Growth and Functional Assaysmentioning

confidence: 99%

“…The presence of several FGFR1 isoforms generated by alternative mRNA splicing makes the analysis of FGFR1 and SPARC interactions difficult. FGF actions strongly depend on the presence of specific FGFR isoforms and can be modulated by changes in isoform expression (Ornitz et al, 1996;Kornmann et al, 2001;Liu et al, 2007a). Alternative splicing of the second half of Ig-like domain III generates particular important isoforms, because this region determines ligand-binding specificity (Ornitz et al, 1996;Plotnikov et al, 2000).…”

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Inhibition of endogenous SPARC enhances pancreatic cancer cell growth: modulation by FGFR1-III isoform expression

et al. 2009

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BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is a multi-faceted protein-modulating cell -cell and cell -matrix interactions. In cancer, SPARC can be not only associated with a highly aggressive phenotype, but also acts as a tumour suppressor. The aim of this study was to characterise the function of SPARC and its modulation by fibroblast growth factor receptor (FGFR) 1 isoforms in pancreatic ductal adenocarcinoma (PDAC). METHODS AND RESULTS: Exogenous SPARC inhibited growth, movement, and migration. ShRNA inhibition of endogenous SPARC in ASPC-1 and PANC-1 cells resulted in increased anchorage-dependent and -independent growth, transwell migration, and xenograft growth as well as increased mitogenic efficacy of fibroblast growth factor (FGF) 1 and FGF2. Endogenous SPARC expression in PANC-1 cells was increased in FGFR1-IIIb over-expressing cells, but decreased in FGFR1-IIIc over-expressing cells. The up-regulation of endogenous SPARC was abrogated by the p38-mitogen-activated protein kinase inhibitor SB203580. SPARC was detectable in conditioned medium of pancreatic stellate cells (PSCs), but not PDAC cells. Conditioned medium of PDAC cells reduced endogenous SPARC expression of PSCs. CONCLUSION: Endogenous SPARC inhibits the malignant phenotype of PDAC cells and may, therefore, act as a tumour suppressor in PDAC. Endogenous SPARC expression can be modulated by FGFR1-III isoform expression. In addition, PDAC cells may inhibit endogenous SPARC expression in surrounding PSCs by paracrine actions.

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Section: Anchorage-dependent Growth and Functional Assaysmentioning

confidence: 99%

Section: Anchorage-dependent Growth and Functional Assaysmentioning

confidence: 99%

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confidence: 99%

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Inhibition of endogenous SPARC enhances pancreatic cancer cell growth: modulation by FGFR1-III isoform expression

et al. 2009

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“…18 A rabbit polyclonal antibody (Flg, c-15 from Santa Cruz) was used (1:200) to detect FGFR1 protein, a mouse monoclonal antibody (clone DCS6 from Biomarkers; 1:200) to detect cyclin D1 protein. Bound antibodies were visualized using enhanced chemiluminescence.…”

Section: Immunoblot Analysis and Kinase Assaymentioning

confidence: 99%

“…16 Similar to the isoforms of FGFR2, the IIIb and IIIc isoforms of FGFR1 have been demonstrated to be functional transmembrane FGFRs. 17,18 In our recent studies, expression of FGFR1-IIIc promoted mitogenic signaling and enhanced pancreatic ductal cell transformation, whereas expression of FGFR1-IIIb inhibited the malignant phenotype of pancreatic cancer cells. 19Y21 Nothing is presently known about the mechanisms regulating the expression of the domain III isoforms of FGFR1.…”

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Exon III Splicing of Fibroblast Growth Factor Receptor 1 Is Modulated by Growth Factors and Cyclin D1

et al. 2008

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Enhanced Expression of Fibroblast Growth Factor Receptor 2 IIIc Promotes Human Pancreatic Cancer Cell Proliferation

Ishiwata

Matsuda

Yamamoto

et al. 2012

The American Journal of Pathology

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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.

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Human Fibroblast Growth Factor Receptor 1-IIIb Is a Functional Fibroblast Growth Factor Receptor Expressed in the Pancreas and Involved in Proliferation and Movement of Pancreatic Ductal Cells

Abstract: Our results demonstrate that the human FGFR-1 IIIb variant is a functional FGFR expressed in the pancreas that can alter pancreatic functions that regulate proliferation, adhesion, and movement.

Cited by 9 publications

References 19 publications

Inhibition of endogenous SPARC enhances pancreatic cancer cell growth: modulation by FGFR1-III isoform expression

Inhibition of endogenous SPARC enhances pancreatic cancer cell growth: modulation by FGFR1-III isoform expression

Exon III Splicing of Fibroblast Growth Factor Receptor 1 Is Modulated by Growth Factors and Cyclin D1

Enhanced Expression of Fibroblast Growth Factor Receptor 2 IIIc Promotes Human Pancreatic Cancer Cell Proliferation

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