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Journal ArticleDOI

Fibroblast growth factors, their receptors and signaling.

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.
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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Citations
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Journal ArticleDOI
TL;DR: The FGF2-FGFR3 axis may promote the progression of esophageal squamous cell carcinoma and may be a new direction of targeted therapy for esoph age-groups with poor prognosis.
Abstract: Background Esophageal squamous cell carcinoma was treated by operation and chemoradiotherapy. However, the prognosis of most patients is poor after treatment, and most studies have shown that FGF2 and its receptor (FGFR) are involved in the development of various malignant tumors. FGF2 plays an important role in tumor progression and malignancy. In this study, the immunohistochemistry of FGF2, FGFR3, and FGFBP1 was used to further verify the expression of the three proteins in 172 patients with esophageal squamous cell carcinoma (ESCC) who had not received preoperative chemoradiotherapy and its effect on the prognosis of ESCC. Methods (1) χ2 test was used to analyze the relationship between proteins and clinicopathological parameters. Survival analysis was used to investigate the effect of three proteins on prognosis. (2) Paired sample t-test was used to analyze the mRNA expression of the three proteins in fresh ESCC tissues and adjacent normal tissues. Results FGF2 was correlated with tumor size (p = 0.026), gender (p = 0.047), and lymph metastasis (p = 0.007) in ESCC tissues. The high expression of FGFR3 was associated with tumor differentiation (p = 0.043 and p < 0.05), lymph node metastasis (p = 0.078 and p < 0.1), and race (p = 0.033 and p < 0.05). The high expression of FGFBP1 was significantly associated with the degree of tumor differentiation (p = 0.012), age (p = 0.045), and lymph node metastasis (p = 0.032) of ESCC patients. The expression of FGF2, FGFR3, and FGFBP1-mRNA in ESCC tissues was significantly higher than that in adjacent tissues (p < 0.001, p < 0.001, and p = 0.001). Patients with high expression of FGF2, FGFBP1, and FGFR3 had poor prognosis. There was a weak positive correlation between FGF2 and FGFBP1, as well as FGFR. Conclusion The FGF2-FGFR3 axis may promote the progression of esophageal squamous cell carcinoma. The FGF2-FGFR3 axis may be a new direction of targeted therapy for esophageal squamous cell carcinoma. FGF2 and FGFR3 may be used as prognostic markers of esophageal squamous cell carcinoma.

7 citations


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

  • ...It has also been shown to be involved in tumorigenesis and angiogenesis [13]....

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  • ...As FGF binds to FGFRs, the tyrosine kinase domain in the cytoplasmic region of the receptors is activated and generates signal paths, such as the Ras-MAPK, PI3KAKT, and PLC-γ-PKC pathways to induce cell proliferation, differentiation, migration, and tumor formation [13]....

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Book ChapterDOI
TL;DR: The purity of SCs collected by Percoll density gradient centrifugation using real-time RT-qPCR and immunocytochemistry for desmin was nearly 90%, which was comparable to that achieved with the conventional method using middle-aged rats.
Abstract: Satellite cells (SCs) are myogenic stem cells that play an important role in skeletal muscle regeneration and hypertrophy. Primary cultures of SCs are useful to analyze cell functions; however, it is difficult to obtain highly pure SCs from young rats with the conventional procedures. The purpose of this study is to establish a purification method for SC isolation from young rats and quantitatively evaluate the purification procedure employing Percoll, a common research tool to purify cells. We elucidated the purity of SCs collected by Percoll density gradient centrifugation using real-time RT-qPCR and immunocytochemistry for desmin. Percoll treatment increased the purity of SCs isolated from young rats to nearly 90%, which was comparable to that achieved with the conventional method using middle-aged rats.

7 citations

Journal ArticleDOI
TL;DR: In this paper, a cross-regulation between FGFR, TGFβ, and PI3K/AKT pathways was shown to regulate Postn expression in breast cancer cells.
Abstract: Breast cancer is a highly heterogeneous disease with multiple drivers and complex regulatory networks. Periostin (Postn) is a matricellular protein involved in a plethora of cancer types and other diseases. Postn has been shown to be involved in various processes of tumor development, such as angiogenesis, invasion, cell survival and metastasis. The expression of Postn in breast cancer cells has been correlated with a more aggressive phenotype. Despite extensive research, it remains unclear how epithelial cancer cells regulate Postn expression. Using murine tumor models and human TMAs, we have assessed the proportion of tumor samples that have acquired Postn expression in tumor cells. Using biochemical approaches and tumor cell lines derived from Neu+ murine primary tumors, we have identified major regulators of Postn gene expression in breast cancer cell lines. Here, we show that, while the stromal compartment typically always expresses Postn, about 50% of breast tumors acquire Postn expression in the epithelial tumor cells. Furthermore, using an in vitro model, we show a cross-regulation between FGFR, TGFβ and PI3K/AKT pathways to regulate Postn expression. In HER2-positive murine breast cancer cells, we found that basic FGF can repress Postn expression through a PKC-dependent pathway, while TGFβ can induce Postn expression in a SMAD-independent manner. Postn induction following the removal of the FGF-suppressive signal is dependent on PI3K/AKT signaling. Overall, these results reveal a novel regulatory mechanism and shed light on how breast tumor cells acquire Postn expression. This complex regulation is likely to be cell type and cancer specific as well as have important therapeutic implications.

7 citations

Journal ArticleDOI
30 Mar 2020
TL;DR: Comprehensive assessment of the epidemiological data on the prevalence of varicose veins and risk factors, of the findings from genetic studies, of data on molecular-cell interactions as well as results of various surgical interventions in patients with varicOSE veins, shows that remodeling is a reversible process that can be stopped and reversed by different stimuli including some chemical substances.
Abstract: Varicose veins of the lower limbs are one of the most common and wide-spread pathology all around the world. What triggers the specific changes in a vein wall still remains unclear as well as what happens in the layers of the vein wall after the disease starts. The aim of the article is to analyze published data and results of researches on epidemiology, genetics, cellular and molecular mechanisms underlying varicose veins pathogenesis. It is now commonly accepted that vein wall changes in patients with varicose veins result from vein-specific inflammation. This process includes leukocytes adhesion to venous endothelium with their subsequent migration into the vein wall and surrounding tissues. Activated leukocytes express a number of molecules that lead to vein wall remodeling and dilation. Comprehensive assessment of the epidemiological data on the prevalence of varicose veins and risk factors, of the findings from genetic studies, of data on molecular-cell interactions as well as results of various surgical interventions in patients with varicose veins, shows that remodeling is a reversible process that can be stopped and reversed by different stimuli including some chemical substances. For the first time in the literature, the authors assume that varicose veins can be successfully cured pharmacologically with no surgical interventions needed.

7 citations


Additional excerpts

  • ...Этот фактор участвует в регуляции пролиферации, дифференцировки клеток и их миграции, контролирует экспрессию компонентов внеклеточного матрикса и матриксных металлопротеиназ [23]....

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Book ChapterDOI
01 Jan 2018
TL;DR: Proteolytic enzymes comprise a group of hydrolases (EC 3.4, NC-IUBMB) which share the common feature of acting on peptide bonds and are among the best-studied enzymes in terms of structure–function relationship.
Abstract: Proteolytic enzymes (proteases) comprise a group of hydrolases (EC 3.4, NC-IUBMB) which share the common feature of acting on peptide bonds. Proteases are among the best-studied enzymes in terms of structure–function relationship (Krowarsch et al. 2005). Proteases, by catalyzing the cleavage of other proteins and even themselves, have an enormous physiological significance, their coding genes representing as much as 2% of the total human genome (Schilling and Overall 2008).

7 citations

References
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Journal ArticleDOI
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.

2,448 citations

Journal ArticleDOI
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.
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.

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 ArticleDOI
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.
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.

2,364 citations

Journal ArticleDOI
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.

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 ArticleDOI

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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