Fibroblast growth factors, their receptors and signaling.

doi:10.1677/ERC.0.0070165

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Fibroblast growth factors, their receptors and signaling.

Journal Article•DOI•

Fibroblast growth factors, their receptors and signaling.

Ciaran Powers¹, S W McLeskey, Anton Wellstein¹•Institutions (1)

Georgetown University¹

01 Sep 2000-Endocrine-related Cancer (Bioscientifica Ltd)-Vol. 7, Iss: 3, pp 165-197

TL;DR: FGF signaling also appears to play a role in tumor growth and angiogenesis, and autocrine FGF signaling may be particularly important in the progression of steroid hormone-dependent cancers to a hormone-independent state.

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Abstract: Fibroblast growth factors (FGFs) are small polypeptide growth factors, all of whom share in common certain structural characteristics, and most of whom bind heparin avidly. Many FGFs contain signal peptides for secretion and are secreted into the extracellular environment, where theycan bind to the heparan-like glycosaminoglycans (HLGAGs) of the extracellular matrix (ECM). From this reservoir, FGFs mayact directlyon target cells, or theycan be released through digestion of the ECM or the activityof a carrier protein, a secreted FGF binding protein. FGFs bind specific receptor tyrosine kinases in the context of HLGAGs and this binding induces receptor dimerization and activation, ultimatelyresulting in the activation of various signal transduction cascades. Some FGFs are potent angiogenic factors and most playimportant roles in embry onic development and wound healing. FGF signaling also appears to playa role in tumor growth and angiogenesis, and autocrine FGF signaling maybe particularlyimportant in the progression of steroid hormone-dependent cancers to a hormone-independent state.

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Journal Article•DOI•

Growth Factor Mediated Signaling in Pancreatic Pathogenesis

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Debashis Nandy¹, Debabrata Mukhopadhyay•Institutions (1)

Mayo Clinic¹

24 Feb 2011-Cancers

TL;DR: The role of different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are discussed and the crosstalk between different growth factors and their respectively signaling mechanisms are discussed.

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Abstract: Functionally, the pancreas consists of two types of tissues: exocrine and endocrine Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide Most pancreatic cancers develop in the exocrine tissues Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

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29 citations

Cites background from "Fibroblast growth factors, their re..."

...The fibroblast growth factor (FGF) family consists of a group of homologous growth-promoting polypeptides [76–80], which enhance tumor growth, angiogenesis, and progression [77–80]....
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...chemotaxis, and sustainability of the enhanced malignant growth [34,78–80,82]....
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Journal Article•DOI•

Correlation of bFGF expression in renal cell cancer with clinical and histopathological features by tissue microarray analysis and measurement of serum levels.

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M. Horstmann¹, Axel S. Merseburger¹, E. von der Heyde, Jürgen Serth, G. Wegener, Michael Mengel, Gerhard Feil¹, Joerg Hennenlotter¹, Udo Nagele¹, Aristotelis G. Anastasiadis¹, Carsten Bokemeyer², Arnulf Stenzl¹, M.A. Kuczyk¹ - Show less +9 more•Institutions (2)

University of Tübingen¹, University of Hamburg²

04 Aug 2005-Journal of Cancer Research and Clinical Oncology

TL;DR: Not the expression of bFGF in the primary tumour but in its invasion front reflects the aggressiveness of RCC, hereby indicating a different biological potential within both areas.

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Abstract: The prognostic value of bFGF for surgically treated renal cell cancer (RCC) patients was evaluated by immunohistochemistry (IHC) and the tissue microarray technique (TMA). Additionally, preoperative serum bFGF levels were correlated to tumour stage and the presence of metastases at initial diagnosis. Serum levels of bFGF were measured by ELISA in 39 healthy volunteers, in 37 patients with benign urologic diseases and in 74 RCC patients, 26 of whom revealed lymph node or distant metastases. bFGF expression as detected by IHC was investigated in 777 tissue cores from 259 different RCC patients [median follow-up: 138 (36-240) months]. Eighty eight patients died from tumour progression. For each patient, the TMA slides contained a tissue core from the primary tumour, its invasion front and the normal renal parenchyma. bFGF serum levels were higher in RCC patients vs healthy volunteers (P<0.01) and vs patients with benign urologic diseases (P<0.01). Metastasized patients revealed higher bFGF serum levels than organ-confined specimens (P<0.01). As detected by IHC only increased bFGF expression in the invasion front tissue correlated with the patients' long-term survival (log rank test) (P=0.03). In multivariate analysis regional LN metastases (P<0.01), the histological grading (P<0.01), and an increased bFGF expression in the invasion front (P=0.04) independently predicted the patients' clinical prognosis. Not the expression of bFGF in the primary tumour but in its invasion front reflects the aggressiveness of RCC, hereby indicating a different biological potential within both areas. The value of bFGF serum levels as indicators of systemic tumour dissemination remains to be determined.

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29 citations

Cites background from "Fibroblast growth factors, their re..."

...FGFs mediate their signals through binding to and activation of cell surface receptors (Powers et al. 2000)....
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...Altered FGF function was demonstrated to stimulate processes involved in cell proliferation and angiogenesis and to inhibit apoptotic pathways (Powers et al. 2000; Ornitz and Itoh 2001)....
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Journal Article•DOI•

Angiogenic activity in patients with psoriasis is significantly decreased by Goeckerman’s therapy

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Ctirad Andrys¹, Lenka Borska¹, David Pohl¹, Zdenek Fiala¹, K. Hamakova¹, Jan Krejsek¹ - Show less +2 more•Institutions (1)

Charles University in Prague¹

13 Jan 2007-Archives of Dermatological Research

TL;DR: It is found that the angiogenic potential which is abnormally increased in patients with psoriasis is significantly alleviated by GT.

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Abstract: Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Goeckerman's therapy is still the first line therapy of psoriasis in the Czech Republic because of its low cost and long-term efficacy. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. An abnormal spectrum of cytokines, growth factors and proangiogenic mediators is produced by keratinocytes and inflammatory cells in patients suffering from the disease. The aim of this study was to evaluate the influence of GT of psoriasis on angiogenic activities by comparing serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 44 patients with psoriasis in peripheral blood samples collected before and after therapy. Forty otherwise healthy blood donors serve as a control group. The efficacy of GT was delineated by psoriasis area and severity index (PASI). The disease activity was significantly diminished by GT (P < 0.001). The serum levels of both VEGF and bFGF were statistically significantly correlated to PASI value in patients before the treatment by GT. The serum levels of VEGF (329.4 +/- 125.5 microg/ml) and bFGF (10.2 +/- 5.04 pg/ml) in patients before GT were significantly higher than those measured in healthy blood donors (VEGF 236.4 +/- 55.9 pg/ml, bFGF 7.3 +/- 3.7 pg/ ml). The serum levels of both VEGF and bFGF were significantly diminished by GT. The level of VEGF dropped from 329.4 +/- 125.5 pg/ml before GT to 278.5 +/- 109.9 pg/ml after GT (P = 0.0042) and the level of bFGF fell from 10.2 +/- 5.04 to 7.78 +/- 4.5 pg/ml (P = 0.019). Comparing to healthy controls, the serum level of bFGF in psoriasis patients was normalised (P = 0.5723) after GT. In contrast, the serum level of VEGF remained significantly increased in psoriasis patients after GT in comparison with healthy blood donors (P = 0.0319). In conclusion, we found that the angiogenic potential which is abnormally increased in patients with psoriasis is significantly alleviated by GT.

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29 citations

Cites background from "Fibroblast growth factors, their re..."

...interactions involving cytokines, growth and diVerentiation factors, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and various products of blood coagulation and Wbrinolysis [12, 14, 23]....
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...Highly sophisticated process of angiogenesis is carefully regulated by numerous intimate cell-to-cell contacts and humoral interactions involving cytokines, growth and diVerentiation factors, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and various products of blood coagulation and Wbrinolysis [12, 14, 23]....
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Journal Article•DOI•

Expression and localization of fibroblast growth factor (FGF) family in buffalo ovarian follicle during different stages of development and modulatory role of FGF2 on steroidogenesis and survival of cultured buffalo granulosa cells.

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S.R. Mishra¹, N. Thakur¹, Anjali Somal¹, Mehtab S. Parmar¹, R. Reshma¹, G. Rajesh¹, Vibha Yadav¹, M.K. Bharti¹, Jaya Bharati¹, Avishek Paul¹, V.S. Chouhan¹, G. T. Sharma¹, Gurmej Singh¹, Mihir Sarkar¹ - Show less +10 more•Institutions (1)

Indian Veterinary Research Institute¹

01 Oct 2016-Research in Veterinary Science

TL;DR: The findings indicate that FGF family members are expressed in a regulated manner in buffalo ovarian follicles during different stages of development where FGF2 may promote steroidogenesis and GC survival through autocrine and paracrine manner.

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29 citations

Cites background from "Fibroblast growth factors, their re..."

...Alternative mRNA splicing in the extracellular domain of FGFR1 to FGFR3 generates receptor variants (IIIB and IIIC)with different ligand-binding affinity (Powers et al., 2000; Bottcher and Niehrs, 2005)....
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...Fibroblast growth factor (FGF) family comprises of 23 closely related members characterized by a well conserved central domain which mediate their biological activities through high-affinity transmembrane receptor tyrosine kinase (RTK), FGFR1 to FGFR4 (Powers et al., 2000; Itoh and Ornitz, 2004; Bottcher and Niehrs, 2005; Zhang et al., 2006; Oulion et al., 2012)....
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...…members characterized by a well conserved central domain which mediate their biological activities through high-affinity transmembrane receptor tyrosine kinase (RTK), FGFR1 to FGFR4 (Powers et al., 2000; Itoh and Ornitz, 2004; Bottcher and Niehrs, 2005; Zhang et al., 2006; Oulion et al., 2012)....
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Journal Article•DOI•

Biocompatibility and bioactivity of designer self-assembling nanofiber scaffold containing FGL motif for rat dorsal root ganglion neurons

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Zhenwei Zou¹, Qixin Zheng¹, Yongchao Wu¹, Xiaodong Guo¹, Shuhua Yang¹, Jingfeng Li¹, Haitao Pan¹ - Show less +3 more•Institutions (1)

Huazhong University of Science and Technology¹

15 Dec 2010-Journal of Biomedical Materials Research Part A

TL;DR: The results indicate that the designer peptide scaffold containing FGL had excellent biocompatibility and bioactivity with adult sensory neurons and could be used for neuronal regeneration.

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Abstract: We report here a designer self-assembling peptide nanofiber scaffold developed specifically for nerve tissue engineering. We synthesized a peptide FGL-RADA containing FGL (EVYVVAENQQGKSKA), the motif of neural cell adhesion molecule (NCAM), and then attended to make a FGL nanofiber scaffold (FGL-NS) by assembling FGL-RADA with the peptide RADA-16 (AcN-RADARADARADARADA-CONH2). The microstructures of the scaffolds were tested using atomic force microscopy (AFM), and rheological properties of materials were accessed. Then we demonstrated the biocompatibility and bioactivity of FGL-NS for rat dorsal root ganglion neurons (DRGn). We found that the designer self-assembling peptide scaffold was noncytotoxic to neurons and able to promote adhesion and neurite sprouting of neurons. Our results indicate that the designer peptide scaffold containing FGL had excellent biocompatibility and bioactivity with adult sensory neurons and could be used for neuronal regeneration.

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29 citations

Cites background from "Fibroblast growth factors, their re..."

...Fibroblast growth factors (FGFs) have been regarded as key regulators of morphogenesis, development, angiogenesis, and wound healing.(24) Recently there have been evidences indicating that FGFs play an important role in the functioning of the peripheral and central neural system....
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References

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Journal Article•DOI•

Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.

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Avner Yayon¹, Michael Klagsbrun², Jeffrey D. Esko³, Philip Leder⁴, David M. Ornitz⁴ - Show less +1 more•Institutions (4)

Weizmann Institute of Science¹, Harvard University², University of Alabama at Birmingham³, Howard Hughes Medical Institute⁴

22 Feb 1991-Cell

TL;DR: It is demonstrated that free heparin and heparan sulfate can reconstitute a low affinity receptor that is, in turn, required for the high affinity binding of bFGF.

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2,448 citations

Journal Article•DOI•

Protein modules and signalling networks

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Tony Pawson¹•Institutions (1)

Mount Sinai Hospital, Toronto¹

16 Feb 1995-Nature

TL;DR: This work highlights conserved protein domains that act as key regulatory participants in many of these different signalling pathways in multicellular organisms.

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Abstract: Communication between cells assumes particular importance in multicellular organisms. The growth, migration and differentiation of cells in the embryo, and their organization into specific tissues, depend on signals transmitted from one cell to another. In the adult, cell signalling orchestrates normal cellular behaviour and responses to wounding and infection. The consequences of breakdowns in this signalling underlie cancer, diabetes and disorders of the immune and cardiovascular systems. Conserved protein domains that act as key regulatory participants in many of these different signalling pathways are highlighted.

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2,433 citations

"Fibroblast growth factors, their re..." refers background in this paper

...One way these recruited target proteins may be localized to the activated receptor is through the interaction between their Src-homology 2 (SH2) domains and specific phosphotyrosine residues on the activated receptor (Pawson 1995)....
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...Phosphorylated tyrosine residues, in turn, recruit other signaling molecules to the activated receptors and propagate the signal through many possible transduction pathways (Pawson 1995)....
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Journal Article•DOI•

Thalidomide is an inhibitor of angiogenesis.

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Robert J. D'Amato¹, Michael S. Loughnan, Evelyn Flynn, Judah Folkman•Institutions (1)

Harvard University¹

26 Apr 1994-Proceedings of the National Academy of Sciences of the United States of America

TL;DR: Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of Thalidomid-treated embryos.

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Abstract: Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in humans. We have demonstrated that orally administered thalidomide is an inhibitor of angiogenesis induced by basic fibroblast growth factor in a rabbit cornea micropocket assay. Experiments including the analysis of thalidomide analogs revealed that the antiangiogenic activity correlated with the teratogenicity but not with the sedative or the mild immunosuppressive properties of thalidomide. Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of thalidomide-treated embryos. These experiments shed light on the mechanism of thalidomide's teratogenicity and hold promise for the potential use of thalidomide as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.

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2,364 citations

Journal Article•DOI•

Receptor specificity of the fibroblast growth factor family.

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David M. Ornitz¹, Jingsong Xu¹, Jennifer S. Colvin¹, Donald G. McEwen¹, Craig A. MacArthur¹, François Coulier², Guangxia Gao³, Mitchell Goldfarb⁴ - Show less +4 more•Institutions (4)

Washington University in St. Louis¹, French Institute of Health and Medical Research², Columbia University³, Icahn School of Medicine at Mount Sinai⁴

21 Jun 1996-Journal of Biological Chemistry

TL;DR: It is demonstrated that FGF 1 is the only FGF that can activate all FGF receptor splice variants and the relative activity of all the other members of the FGF family is determined.

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2,066 citations

"Fibroblast growth factors, their re..." refers background in this paper

...†From Ornitz et al. (1996), except where stated; ‡From Koga et al. (1995); §From Miralles et al. (1999); ¶From Xu et al. (1999). topologically identical to interleukin-1β (IL-1β) (Zhu et al. 1991), with which some members also share the feature of secretion by an endoplasmic reticulum…...
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...Mutation of all four cysteines to serines results in a protein with the same secondary structure and equally mitogenic for 3T3 cells as the wild-type FGF-2 (Foxet al. 1988), suggesting that the formation of disulfide bridges is not important for the secondary structure and mitogenic activity of…...
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...Ornitz et al. (1996) determined the specificity of different FGFs for different receptor isoforms by overexpressing these isoforms in Baf3 cells, which do not normally express FGFRs, and assaying for [3H]thymidine incorporation in these cells following treatment with different FGFs (see Table 2)....
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...1, IIIb 100 60 34 16 4 5 6 4 4 1, IIIc 100 104 0 102 59 55 0 1 21 2, IIIb 100 9 45 15 5 5 81 4 7 2, IIIc 100 64 4 94 25 61 2.5 16 89 3, IIIb 100 1 2 1 1 1 1 1 42 3, IIIc 100 107 1 69 12 9 1 41 96 4 100 113 6 108 7 79 2 76 75 Modified from Ornitz et al. (1996)....
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Journal Article•DOI•

The heparin-binding (fibroblast) growth factor family of proteins.

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Wilson H. Burgess, Thomas Maciag

01 Jan 1989-Annual Review of Biochemistry

1,994 citations

"Fibroblast growth factors, their re..." refers background in this paper

...Defining features of the FGF family are a strong affinity for heparin and HLGAGs (Burgess & Maciag 1989), as well as a central core of 140 amino acids that is highly homologous between different family members....
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