scholarly journals Fibroblast growth factors activate mitogen-activated protein kinase pathways to promote migration in ovine trophoblast cells

Reproduction ◽  
2011 ◽  
Vol 141 (5) ◽  
pp. 707-714 ◽  
Author(s):  
Qi En Yang ◽  
Mariana I Giassetti ◽  
Alan D Ealy
Keyword(s):  
Cell Migration ◽  
Growth Factors ◽  
Fibroblast Growth Factors ◽  
Mitogen Activated Protein Kinase ◽  
Fibroblast Growth ◽  
Trophoblast Cells ◽  
Migratory Activity ◽  
Mapk Cascades ◽  
Mitogen Activated Protein ◽  
Cattle And Sheep

Fibroblast growth factors (FGFs) 2 and FGF10 are uterine- and conceptus-derived factors that mediate trophoblast activities in cattle and sheep. To extend our understanding of how FGFs may control peri-implantation development in ruminants, we determined whether FGF2 and FGF10 impact trophoblast cell migration. Transwell inserts containing 8 μm pores were used to examine whether FGF2 or FGF10 supplementation increased oTr1 cell migration. Supplementation with 0.5 ng/ml FGF2 or FGF10 did not affect oTr1 cell migration number, but exposure to 5 or 50 ng/ml FGF2 or FGF10 increased (P<0.05) oTr1 cell migration when compared with controls. The involvement of specific MAP kinase (MAPK) cascades in mediating this FGF response was examined by using pharmacological inhibitors of specific MAPKs. Western blot analysis indicated that FGF2 and FGF10 increased phosphorylation status of MAPKs 1, 3, 8, 9, and 14. Exposure to specific inhibitors blocked FGF induction of each MAPK. Exposure to inhibitors before supplementation with FGF2 or FGF10 prevented FGF induction of cell migration, indicating that each of these signaling molecules was required for FGF effects. A final series of studies examined whether FGF2 and FGF10 also mediated the migration of a bovine trophoblast line (CT1 cell). Increases in migration were detected in each cell line by supplementing 5 or 50 ng/ml FGF2 or FGF10 (P<0.05). In summary, FGF2 and FGF10 regulate migratory activity of ovine trophoblast cells through MAPK-dependent pathways. These outcomes provide further evidence that FGFs function as mediators of peri-implantation conceptus development in cattle and sheep.

139 STIMULATION OF BOVINE TROPHECTODERM MIGRATION BY FIBROBLAST GROWTH FACTORS

2010 ◽  
Vol 22 (1) ◽  
pp. 228
Author(s):  
M. I. Giassetti ◽  
Q. E. Yang ◽  
A. D. Ealy
Keyword(s):  
Cell Migration ◽  
Growth Factors ◽  
Fibroblast Growth Factors ◽  
Large Family ◽  
Lower Surface ◽  
Epifluorescence Microscopy ◽  
Receptor Subtypes ◽  
Fibroblast Growth ◽  
Conceptus Development

Following hatching, bovine and ovine blastocysts elongate into tubular and then filamentous conceptuses that remain free-floating for several days before attaching to the uterine lining. Elongation is marked by trophectoderm proliferation and changes in trophectoderm shape. The ultimate goal of this work is to identify uterine- and conceptus-derived factors that control peri-attachment conceptus development in cattle. Fibroblast growth factors (FGF) encompass a large family of mitogens, morphogens, and angiogenic factors produced by various tissues, including the bovine/ovine endometrium and conceptus. FGF2 and FGF10 are of particular interest because uterine production of FGF2 and conceptus production of FGF10 intensify as elongation takes place in cattle and sheep. The objective of this work was to determine if FGF2 and FGF10 stimulate bovine trophectoderm migration during culture. Migration assays were conducted with CT1 cells, a trophectoderm line established from a bovine in vitro-produced blastocyst outgrowth. Cells were seeded on 8-μm pore Transwell inserts (Corning Inc., Corning, NY, USA; 50,000 cells/insert) and submerged in serum-free DMEM containing treatments (0, 0.5, 5, 50, and 500 ng mL-1 of recombinant bovine FGF2 or human FGF10). After 12 h, cells that migrated onto the lower surface were fixed, stained, and processed for counting using epifluorescence microscopy. Migrated cells were counted in 5 non-overlapping locations on each of 4 replicate Transwell inserts for each treatment. Experiments were repeated on at least 3 different occasions. Analysis of variance was completed. Differences in individual means were partitioned further by completing pair-wise comparisons. Supplementation with 5 or 50 ng mL-1 of FGF2 increased (P = 0.06 and P = 0.002, respectively) migration of CT1 cells when compared with controls (327 ± 17 or 485 ± 40 cells, respectively, v. 162 ± 16 cells). Supplementation with 500 ng mL-1 of FGF2 further increased (P < 0.02) migration when compared with controls and cells exposed to lower levels of FGF2 (548 ± 116 cells). FGF10 also stimulated CT1 migration. Supplementation with 0.5 ng mL-1 of FGF10 increased (P = 0.06) cell migration v. controls (254 ± 48 v. 184 ± 24 cells). Supplementation with 5 ng mL-1 further increased (P < 0.007) cell migration (373 ± 29 cells). Exposure to greater FGF10 concentrations did not further enhance cell migration. To summarize, both FGF2 and FGF10 promoted CT1 migration, suggestive of a potential function in regulating trophectoderm development, differentiation, and/or morphogenesis during peri-attachment conceptus development. FGF10 appeared to be more potent than FGF2 at mediating CT1 migration. The reason for this disparity has not been resolved but likely involves differences in ligand affinities to certain receptor subtypes. This project was supported by NRI Competitive Grant No. 2008-35203-19106 from the USDA-CSREES.

scholarly journals Distribution of fibroblast growth factors and their roles in skin fibroblast cell migration

2016 ◽  
Vol 14 (4) ◽  
pp. 3336-3342 ◽  
Author(s):  
Yong Huan Song ◽  
Yu Ting Zhu ◽  
Jian Ding ◽  
Fei Ya Zhou ◽  
Ji Xin Xue ◽  
...  
Keyword(s):  
Cell Migration ◽  
Growth Factors ◽  
Skin Fibroblast ◽  
Fibroblast Growth Factors ◽  
Fibroblast Cell ◽  
Fibroblast Growth

Cytogenetics, Immunostaining for Fibroblast Growth Factors, p53 Sequencing, and Clinical Features of Two Cases of Cystosarcoma Phyllodes

2000 ◽  
Vol 5 (3) ◽  
pp. 179-190 ◽  
Author(s):  
PAUL V. WOOLLEY ◽  
SUSANNE M. GOLLIN ◽  
WAHEEB RISKALLA ◽  
SYDNEY FINKELSTEIN ◽  
DAVID F. STEFANIK ◽  
...  
Keyword(s):  
Growth Factors ◽  
Clinical Features ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Cystosarcoma Phyllodes

Implications of Fibroblast Growth Factors (FGFs) in Cancer: From Prognostic to Therapeutic Applications

2019 ◽  
Vol 20 (8) ◽  
pp. 852-870
Author(s):  
Hassan Dianat-Moghadam ◽  
Ladan Teimoori-Toolabi
Keyword(s):  
Growth Factors ◽  
Wound Repair ◽  
Fibroblast Growth Factors ◽  
Predictive Biomarkers ◽  
Fibroblast Growth ◽  
Loss Of Function ◽  
Cellular Processes ◽  
Fgfr Signaling ◽  
Proliferation And Metastasis ◽  
Immense Potential

Fibroblast growth factors (FGFs) are pleiotropic molecules exerting autocrine, intracrine and paracrine functions via activating four tyrosine kinase FGF receptors (FGFR), which further trigger a variety of cellular processes including angiogenesis, evasion from apoptosis, bone formation, embryogenesis, wound repair and homeostasis. Four major mechanisms including angiogenesis, inflammation, cell proliferation, and metastasis are active in FGF/FGFR-driven tumors. Furthermore, gain-of-function or loss-of-function in FGFRs1-4 which is due to amplification, fusions, mutations, and changes in tumor–stromal cells interactions, is associated with the development and progression of cancer. Although, the developed small molecule or antibodies targeting FGFR signaling offer immense potential for cancer therapy, emergence of drug resistance, activation of compensatory pathways and systemic toxicity of modulators are bottlenecks in clinical application of anti-FGFRs. In this review, we present FGF/FGFR structure and the mechanisms of its function, as well as cross-talks with other nodes and/or signaling pathways. We describe deregulation of FGF/FGFR-related mechanisms in human disease and tumor progression leading to the presentation of emerging therapeutic approaches, resistance to FGFR targeting, and clinical potentials of individual FGF family in several human cancers. Additionally, the underlying biological mechanisms of FGF/FGFR signaling, besides several attempts to develop predictive biomarkers and combination therapies for different cancers have been explored.

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