Fibroblast growth factors, their receptors and signaling.
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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TL;DR: This review summarizes the current knowledge on the testicular occurrence and expression pattern of members of the plasminogen activation system and the various predicted functions for these molecules in the establishment and maintenance of thetesticular architecture and in the process of spermatogenesis.
Abstract: The testis is an organ in which a series of radical remodeling events occurs during development and in adult life. These events likely rely on a sophisticated network of proteases and complementary inhibitors, including the plasminogen activation system. This review summarizes our current knowledge on the testicular occurrence and expression pattern of members of the plasminogen activation system. The various predicted functions for these molecules in the establishment and maintenance of the testicular architecture and in the process of spermatogenesis are presented.
36 citations
TL;DR: In vivo, antisense perlecan-transfected cells generated no tumors, whereas untransfected and vector-transferred cells formed tumors with obvious neovascularization, suggesting that tumor perle can rather than host perleCAN controls tumor growth and angiogenesis.
Abstract: As a major heparan sulfate proteoglycan (PG) in basement membranes, perlecan has been linked to tumor invasion, metastasis, and angiogenesis. Here we produced epidermal tumors in immunocompromised rats by injection of mouse RT101 tumor cells. Tumor sections stained with species-specific perlecan antibodies, together with immunoelectron microscopy, showed that perlecan distributed around blood vessels was of both host and tumor cell origin. Tumor-derived perlecan was also distributed throughout the tumor matrix. Blood vessels stained with rat-specific PECAM-1 antibody showed their host origin. RT101 cells also expressed two other basement membrane heparan sulfate PGs, agrin and type XVIII collagen. Antisense targeting of perlecan inhibited tumor cell growth in vitro, while exogenous recombinant perlecan, but not heparin, restored the growth of antisense perlecan-expressing cells, suggesting that perlecan core protein, rather than heparan sulfate chains from perlecan, agrin, or type XVIII collagen, regulates tumor cell growth. However, perlecan core protein requirement was not related to fibroblast growth factor-7 binding because RT101 cells were unresponsive to and lacked receptors for this growth factor. In vivo, antisense perlecan-transfected cells generated no tumors, whereas untransfected and vector-transfected cells formed tumors with obvious neovascularization, suggesting that tumor perlecan rather than host perlecan controls tumor growth and angiogenesis.
36 citations
Cites background from "Fibroblast growth factors, their re..."
...The biological function of FGF-7 is specifically mediated through FGFR-2 isoform IIIb, which is normally expressed on epithelial cells (reviewed in Powers et al. 2000)....
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TL;DR: A summary of cell senescence and immortalization is provided and advantages and limitations of tissue engineering and regeneration with the use of immortalized cells as well as a potential rejuvenation strategy through combination with the dECM approach are discussed.
Abstract: Cellular senescence is a major hurdle for primary cell-based tissue engineering and regenerative medicine. Telomere erosion, oxidative stress, the expression of oncogenes and the loss of tumor suppressor genes all may account for the cellular senescence process with the involvement of various signaling pathways. To establish immortalized cell lines for research and clinical use, strategies have been applied including internal genomic or external matrix microenvironment modification. Considering the potential risks of malignant transformation and tumorigenesis of genetic manipulation, environmental modification methods, especially the decellularized cell-deposited extracellular matrix (dECM)-based preconditioning strategy, appear to be promising for tissue engineering-aimed cell immortalization. Due to few review articles focusing on this topic, this review provides a summary of cell senescence and immortalization and discusses advantages and limitations of tissue engineering and regeneration with the use of immortalized cells as well as a potential rejuvenation strategy through combination with the dECM approach.
35 citations
TL;DR: Xenopus laevis homolog of LMW-PTP1 is identified as an additional positive regulator in the fibroblast growth factor (FGF) signaling pathway during Xenopus development and revealed as a new and important component of the FGF signaling pathway.
Abstract: Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) has been implicated in the regulation of cell growth and actin rearrangement mediated by several receptor tyrosine kinases, including platelet-derived growth factor and epidermal growth factor Here we identify the Xenopus laevis homolog of LMW-PTP1 (XLPTP1) as an additional positive regulator in the fibroblast growth factor (FGF) signaling pathway during Xenopus development XLPTP1 has an expression pattern that displays substantial overlap with FGF receptor 1 (FGFR1) during Xenopus development Using morpholino antisense technology, we show that inhibition of endogenous XLPTP1 expression dramatically restricts anterior and posterior structure development and inhibits mesoderm formation In ectodermal explants, loss of XLPTP1 expression dramatically blocks the induction of the early mesoderm gene, Xbrachyury (Xbra), by FGF and partially blocks Xbra induction by Activin Moreover, FGF-induced activation of mitogen-activated protein (MAP) kinase is also inhibited by XLPTP1 morpholino antisense oligonucleotides; however, introduction of RNA encoding XLPTP1 is able to rescue morphological and biochemical effects of antisense inhibition Inhibition of FGF-induced MAP kinase activity due to loss of XLPTP1 is also rescued by an active Ras, implying that XLPTP1 may act upstream of or parallel to Ras Finally, XLPTP1 physically associates only with an activated FGFR1, and this interaction requires the presence of SNT1/FRS-2 (FGFR substrate 2) Although LMW-PTP1 has been shown to participate in other receptor systems, the data presented here also reveal XLPTP1 as a new and important component of the FGF signaling pathway
35 citations
Cites background from "Fibroblast growth factors, their re..."
...Growing evidence suggests that SNT1/ FRS-2 has a docking function much like that of the insulin receptor substrate (63), and the above data suggest that XLPTP1 may complex with XSNT1 or one of the recruited proteins....
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TL;DR: The data indicate that the guidance functions of these FGFs must act in concert with other important attractive or adhesive activities of the trunk visceral mesoderm, and apart from their guidance functions, the Pyr and Ths signals play an obligatory role for the survival of the migrating cells.
35 citations
References
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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
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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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
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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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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