Basic Fibroblast Growth Factor and Receptor Expression in Human Ovarian Cancer

Crickard, Kent; Gross, Janet L.; Crickard, Ulla; Yoonessi, Mahmood; Lele, Shashikant; Herblin, William F.; Eidsvoog, Kristi

doi:10.1006/gyno.1994.1290

Cited by 62 publications

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“…The gene list defined herein also included several members of the FGF2 signaling pathway, which are known to be expressed in ovarian and EOC cells (Crickard et al, 1994;Di Blasio et al, 1995;Valve et al, 2000), and several other genes regulated by FGF2 in various contexts: CDH11 is specifically regulated by FGF2 in models of kidney fibrosis (Strutz et al, 2002), LUM expression is induced by FGF2 in keratocytes of the corneal stroma (Long et al, 2000), while BGN is similarly controlled in aortic endothelial cells (Kinsella et al, 1997). Coexpression of the latter molecules could also be related to the evidence that FGF family members bind to heparan sulfate proteoglycans of the ECM, with such interaction comprising part of the regulation of the FGF signaling unit (Plotnikov et al, 1999;Plotnikov et al, 2000;Schlessinger et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling of advanced ovarian cancer: characterization of a molecular signature involving fibroblast growth factor 2

et al. 2004

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Epithelial ovarian cancer (EOC) is the gynecological disease with the highest death rate. We applied an automatic class discovery procedure based on gene expression profiling to stages III-IV tumors to search for molecular signatures associated with the biological properties and progression of EOC. Using a complementary DNA microarray containing 4451 cancer-related, sequence-verified features, we identified a subset of EOC characterized by the expression of numerous genes related to the extracellular matrix (ECM) and its remodeling, along with elements of the fibroblast growth factor 2 (FGF2) signaling pathway. A total of 10 genes were validated by quantitative real-time polymerase chain reaction, and coexpression of FGF2 and fibroblast growth factor receptor 4 in tumor cells was revealed by immunohistochemistry, confirming the reliability of gene expression by cDNA microarray. Since the functional relationships among these genes clearly suggested involvement of the identified molecular signature in processes related to epithelial-stromal interactions and/or epithelial-mesenchymal cellular plasticity, we applied supervised learning analysis on ovarian-derived cell lines showing distinct cellular phenotypes in culture. This procedure enabled construction of a gene classifier able to discriminate mesenchymal-like from epithelial-like cells. Genes overexpressed in mesenchymal-like cells proved to match the FGF2 signaling and ECM molecular signature, as identified by unsupervised class discovery on advanced tumor samples. In vitro functional analysis of the cell plasticity classifier was carried out using two isogenic and immortalized cell lines derived from ovarian surface epithelium and displaying mesenchymal and epithelial morphology, respectively. The results indicated the autocrine, but not intracrine stimulation of mesenchymal conversion and cohort/scatter migration of cells by FGF2, suggesting a central role for FGF2 signaling in the maintenance of cellular plasticity of ovary-derived cells throughout the carcinogenesis process. These findings raise mechanistic hypotheses on EOC pathogenesis and progression that might provide a rational underpinning for new therapeutic modalities.

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Section: Discussionmentioning

confidence: 99%

Gene expression profiling of advanced ovarian cancer: characterization of a molecular signature involving fibroblast growth factor 2

et al. 2004

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“…9 Other studies have demonstrated that several other members of the FGF-FGFR family are present and, that in some cases they may have prognostic significance. [10][11][12] However, these studies have evaluated only selected FGFs and FGFRs. Here we present the first comprehensive observational and functional studies of the FGF-FGFR family in epithelial ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of FGFR2 and FGFR1 increases cisplatin sensitivity in ovarian cancer

Cole

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et al. 2010

Cancer Biology & Therapy

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“…In the ovary, little is known about the role of the FGFs in maintenance of the normal OSE and the progression to carcinogenesis. Studies have indicated that ovarian tumours are able to produce FGF-2 (bFGF), a growth factor which can bind to the majority of FGF receptors, some of which are expressed in ovarian cancer (Di Blasio et al, 1993;Crickard et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Induction of FGF receptor 2-IIIb expression and response to its ligands in epithelial ovarian cancer

et al. 2001

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Epithelial ovarian cancers (EOCs) arise in the Ovarian Surface Epithelium (OSE). This tissue is a simple, poorly committed mesothelium which exhibits characteristics of epithelial and mesenchymal cells when grown in culture. In contrast, EOCs frequently exhibit properties of complex epithelial tissues of the female reproductive tract, such as oviductal, endometrial and cervical epithelia, and show induction of expression of epithelial markers such as E-cadherin. Fibroblast Growth Factor Receptor 2 isoform IIIb (FGF receptor 2-IIIb) is a spliced variant of FGF receptor 2 that binds the ligands FGF-1 and FGF-7 with high a nity, and is expressed exclusively by epithelial cells. We have studied the expression of FGF receptor 2-IIIb and its ligands in primary cultures of normal human OSE, EOC cell lines and snap frozen tissue from EOCs. Expression of FGF receptor 2-IIIb mRNA is undetectable in normal OSE, but is expressed in 16/20 (80%) of EOCs. FGFs 1 and 7 mRNAs are expressed in normal OSE, whilst only 4/20 (20%) and 12/20 (60%) of EOCs demonstrated expression for these ligands respectively. However, FGF-7 protein was detected in 70% (mean level=0.7 ng/ml) of ascitic¯uids obtained from patients with EOC. FGFs 1 and 7 stimulate DNA synthesis in EOC cell lines that express FGF receptor 2-IIIb. Moreover, DNA synthesis in these cell lines can be partially blocked by blocking antisera to FGFs 1 and 7. It is suggested that induction of expression of FGF receptor 2-IIIb may play a role in the development of EOCs by rendering the OSE susceptible to paracrine and/or autocrine stimulation by its requisite FGF ligands. Oncogene (2001) 20, 5878 ± 5887.

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Basic Fibroblast Growth Factor and Receptor Expression in Human Ovarian Cancer

Cited by 62 publications

References 0 publications

Gene expression profiling of advanced ovarian cancer: characterization of a molecular signature involving fibroblast growth factor 2

Gene expression profiling of advanced ovarian cancer: characterization of a molecular signature involving fibroblast growth factor 2

Inhibition of FGFR2 and FGFR1 increases cisplatin sensitivity in ovarian cancer

Induction of FGF receptor 2-IIIb expression and response to its ligands in epithelial ovarian cancer

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