IIIc isoform of fibroblast growth factor receptor 1 is overexpressed in human pancreatic cancer and enhances tumorigenicity of hamster ductal cells

Kornmann, Marko; Ishiwata, Toshiyuki; Matsuda, Kei; Lopez, Martha E.; Fukahi, Kimi; Asano, Gorō; Beger, H. G.; Korc, Murray

doi:10.1053/gast.2002.34174

Cited by 36 publications

(64 citation statements)

References 44 publications

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“…All cell lines used in our study expressed various levels of FGFR1 (Kornmann et al, 2002). Inhibition of FGF1-induced proliferation by exogenous SPARC was enhanced in FGFR1-III over-expressing cells compared with controls.…”

Section: Discussionmentioning

confidence: 96%

“…Another reason contributing to the down-regulation of SPARC in human pancreatic cancer cells may be the over-expression of FGFR1-IIIc. FGFR1-IIIc is the predominant FGFR1 isoform expressed in PDAC (Kornmann et al, 2002). FGFR1-IIIb usually expressed in cells of epithelial origin is almost absent in PDAC (Kornmann et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Basal anchorage-independent cell growth was assessed by a double-layer soft-agar assay as described (Kornmann et al, 2002). Briefly, cells were suspended in complete medium containing 0.3% agar and seeded in triplicate in six-well plates onto a base layer of complete medium containing 0.5% agar.…”

Section: Anchorage-independent Growth Assaymentioning

confidence: 99%

“…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). As a consequence, overexpression of FGFR1-IIIc in pancreatic cancer promoted tumourigenesis, whereas over-expression of FGFR1-IIIb inhibited the malignant phenotype (Kornmann et al, 2002;Liu et al, 2007b). In addition, several FGFs, signalling through FGFR1-IIIc, are highly over-expressed in human pancreatic ductal adenocarcinoma (PDAC) (Yamanaka et al, 1993).…”

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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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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: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Anchorage-independent Growth Assaymentioning

confidence: 99%

mentioning

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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“…A growing line of evidence has shown that various FGFs, such as FGF-1, FGF-2, FGF-5, FGF-7 (66-69) and FGF receptors (70)(71)(72)(73) are upregulated in pancreatic cancer tissue samples and cell lines. These findings suggest that FGF-dependent downstream biologic events are likely to play an important role in the pathobiology of pancreatic cancer.…”

Section: Angiogenesis In Gastrointestinal Cancersmentioning

confidence: 99%

The Angiogenic Switch Molecule, Secreted FGF-Binding Protein, an Indicator of Early Stages of Pancreatic and Colorectal Adenocarcinoma

Tassi

Wellstein

2006

Seminars in Oncology

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Tumor angiogenesis has been related to the initiation as well as progression toward more aggressive behavior of human tumors. We will discuss genetic events underlying the initiation and progression of colorectal and pancreatic adenocarcinoma with a particular focus on the modulation of angiogenesis. A secreted fibroblast growth factor (FGF) binding protein (FGF-BP), which is an extracellular chaperone molecule for FGFs, has been shown to enhance FGF-mediated biochemical and biologic events and to be a crucial rate-limiting factor for tumor-dependent angiogenesis. Histochemical and in situ hybridization studies with archival samples show that FGF-BP is induced early during the initiation of colorectal and pancreatic adenocarcinoma. We will discuss the potential of this secreted protein as a serum marker to identify at-risk subjects.

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Nuclear translocation of FGFR1 and FGF2 in pancreatic stellate cells facilitates pancreatic cancer cell invasion

et al. 2014

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Pancreatic cancer is characterised by desmoplasia, driven by activated pancreatic stellate cells (PSCs). Over-expression of FGFs and their receptors is a feature of pancreatic cancer and correlates with poor prognosis, but whether their expression impacts on PSCs is unclear. At the invasive front of human pancreatic cancer, FGF2 and FGFR1 localise to the nucleus in activated PSCs but not cancer cells. In vitro, inhibiting FGFR1 and FGF2 in PSCs, using RNAi or chemical inhibition, resulted in significantly reduced cell proliferation, which was not seen in cancer cells. In physiomimetic organotypic co-cultures, FGFR inhibition prevented PSC as well as cancer cell invasion. FGFR inhibition resulted in cytoplasmic localisation of FGFR1 and FGF2, in contrast to vehicle-treated conditions where PSCs with nuclear FGFR1 and FGF2 led cancer cells to invade the underlying extra-cellular matrix. Strikingly, abrogation of nuclear FGFR1 and FGF2 in PSCs abolished cancer cell invasion. These findings suggest a novel therapeutic approach, where preventing nuclear FGF/FGFR mediated proliferation and invasion in PSCs leads to disruption of the tumour microenvironment, preventing pancreatic cancer cell invasion.

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IIIc isoform of fibroblast growth factor receptor 1 is overexpressed in human pancreatic cancer and enhances tumorigenicity of hamster ductal cells

Cited by 36 publications

References 44 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

The Angiogenic Switch Molecule, Secreted FGF-Binding Protein, an Indicator of Early Stages of Pancreatic and Colorectal Adenocarcinoma

Nuclear translocation of FGFR1 and FGF2 in pancreatic stellate cells facilitates pancreatic cancer cell invasion

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