Induction of chondrogenesis in neural crest cells by mutant fibroblast growth factor receptors

2002 ◽  
Vol 224 (2) ◽  
pp. 210-221 ◽  
Author(s):  
Anita Petiot ◽  
Patrizia Ferretti ◽  
Andrew J. Copp ◽  
Chi-Tsung Joseph Chan
Keyword(s):  
Growth Factor ◽  
Neural Crest ◽  
Fibroblast Growth Factor ◽  
Neural Crest Cells ◽  
Growth Factor Receptors ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Receptors

scholarly journals Targeting fibroblast growth factor receptors to combat aggressive ependymoma

2021 ◽  
Author(s):  
Daniela Lötsch ◽  
Dominik Kirchhofer ◽  
Bernhard Englinger ◽  
Li Jiang ◽  
Konstantin Okonechnikov ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Molecular Mechanisms ◽  
Radial Glia ◽  
Growth Factor Receptors ◽  
Dominant Negative ◽  
Mrna Levels ◽  
Fibroblast Growth ◽  
Cell Models ◽  
Fibroblast Growth Factor Receptors

AbstractEpendymomas (EPN) are central nervous system tumors comprising both aggressive and more benign molecular subtypes. However, therapy of the high-risk subtypes posterior fossa group A (PF-A) and supratentorial RELA-fusion positive (ST-RELA) is limited to gross total resection and radiotherapy, as effective systemic treatment concepts are still lacking. We have recently described fibroblast growth factor receptors 1 and 3 (FGFR1/FGFR3) as oncogenic drivers of EPN. However, the underlying molecular mechanisms and their potential as therapeutic targets have not yet been investigated in detail. Making use of transcriptomic data across 467 EPN tissues, we found that FGFR1 and FGFR3 were both widely expressed across all molecular groups. FGFR3 mRNA levels were enriched in ST-RELA showing the highest expression among EPN as well as other brain tumors. We further identified high expression levels of fibroblast growth factor 1 and 2 (FGF1, FGF2) across all EPN subtypes while FGF9 was elevated in ST-EPN. Interrogation of our EPN single-cell RNA-sequencing data revealed that FGFR3 was further enriched in cycling and progenitor-like cell populations. Corroboratively, we found FGFR3 to be predominantly expressed in radial glia cells in both mouse embryonal and human brain datasets. Moreover, we detected alternative splicing of the FGFR1/3-IIIc variant, which is known to enhance ligand affinity and FGFR signaling. Dominant-negative interruption of FGFR1/3 activation in PF-A and ST-RELA cell models demonstrated inhibition of key oncogenic pathways leading to reduced cell growth and stem cell characteristics. To explore the feasibility of therapeutically targeting FGFR, we tested a panel of FGFR inhibitors in 12 patient-derived EPN cell models revealing sensitivity in the low-micromolar to nano-molar range. Finally, we gain the first clinical evidence for the activity of the FGFR inhibitor nintedanib in the treatment of a patient with recurrent ST-RELA. Together, these preclinical and clinical data suggest FGFR inhibition as a novel and feasible approach to combat aggressive EPN.

Semirational design of a potent, artificial agonist of fibroblast growth factor receptors

10.1038/70746 ◽  
1999 ◽  
Vol 17 (12) ◽  
pp. 1199-1204 ◽  
Author(s):  
Marcus D. Ballinger ◽  
Venkatakrishna Shyamala ◽  
Louise D. Forrest ◽  
Maja Deuter-Reinhard ◽  
Laura V. Doyle ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptors ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Receptors

scholarly journals Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration

2021 ◽  
Vol 22 (15) ◽  
pp. 7867
Author(s):  
Marlena Typiak ◽  
Tomasz Kulesza ◽  
Patrycja Rachubik ◽  
Dorota Rogacka ◽  
Irena Audzeyenka ◽  
...  
Keyword(s):  
Growth Factor ◽  
Urinary Excretion ◽  
Glomerular Filtration ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptors ◽  
Renal Tissue ◽  
Proper Function ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Receptors ◽  
Plasma Filtration

Hyperglycemic conditions (HG), at early stages of diabetic nephropathy (DN), cause a decrease in podocyte numbers and an aberration of their function as key cells for glomerular plasma filtration. Klotho protein was shown to overcome some negative effects of hyperglycemia. Klotho is also a coreceptor for fibroblast growth factor receptors (FGFRs), the signaling of which, together with a proper rate of glycolysis in podocytes, is needed for a proper function of the glomerular filtration barrier. Therefore, we measured levels of Klotho in renal tissue, serum, and urine shortly after DN induction. We investigated whether it influences levels of FGFRs, rates of glycolysis in podocytes, and albumin permeability. During hyperglycemia, the level of membrane-bound Klotho in renal tissue decreased, with an increase in the shedding of soluble Klotho, its higher presence in serum, and lower urinary excretion. The addition of Klotho increased FGFR levels, especially FGFR1/FGFR2, after their HG-induced decrease. Klotho also increased levels of glycolytic parameters of podocytes, and decreased podocytic and glomerular albumin permeability in HG. Thus, we found that the decrease in the urinary excretion of Klotho might be an early biomarker of DN and that Klotho administration may have several beneficial effects on renal function in DN.

BHK-21-derived cell lines that produce basic fibroblast growth factor, but not parental BHK-21 cells, initiate neuronal differentiation of neural crest progenitors

Development ◽  
1992 ◽  
Vol 115 (4) ◽  
pp. 1059-1069 ◽  
Author(s):  
G. Brill ◽  
N. Vaisman ◽  
G. Neufeld ◽  
C. Kalcheim
Keyword(s):  
Growth Factor ◽  
Neural Crest ◽  
Fibroblast Growth Factor ◽  
Neuronal Differentiation ◽  
Cell Lines ◽  
Basic Fibroblast Growth Factor ◽  
Neural Crest Cells ◽  
Fibroblast Growth ◽  
Similar Treatment ◽  
Bhk Cells

We present evidence that basic fibroblast growth factor (bFGF)-producing cells stimulate primary differentiation of neurons from neural crest progenitors. Baby hamster kidney (BHK-21) cells were stably cotransfected with plasmid pSV2/neo, which contains the gene conferring resistance to the neomycin analog G418 and expression vectors containing the human bFGF cDNA. Various clones, which differed in their bFGF production levels, were isolated. Homogeneous neural crest cells were cultured on monolayers of bFGF-producing, BHK-21-derived cell lines. While the parental BHK-21 cells, which do not produce detectable bFGF, had poor neurogenic ability, the various bFGF-producing clones promoted a 1.5- to 4-fold increase in neuronal cell number compared to the parental cells. This increase was correlated with the levels of bFGF produced by the different transfected clones, which ranged between 2.3 and 140 ng/mg protein. In contrast, no stimulation of neuronal differentiation was observed when neural crest cells were grown on monolayers of parental BHK cells transfected with plasmid pSV2/neo alone, or on a parental BHK-derived clone, which secretes high amounts of recombinant vascular endothelial growth factor (VEGF). Furthermore, the neuron-promoting ability of bFGF-producing cells could be mimicked by addition of exogenous bFGF to neural crest cells grown on the parental BHK line. A similar treatment of neural crest cells grown on laminin substrata, instead of BHK cells, resulted in increased survival of non-neuronal cells, but not of neurons (see also Kalcheim, C. 1989, Dev. Biol. 134, 1–10). Taken together, these results suggest that bFGF stimulates neuronal differentiation of neural crest cells by a cell-mediated signalling mechanism.

Mapping of Murine Fibroblast Growth Factor Receptors Refines Regions of Homology between Mouse and Human Chromosomes

Genomics ◽  
1994 ◽  
Vol 21 (3) ◽  
pp. 656-658 ◽  
Author(s):  
Karen B. Avraham ◽  
David Givol ◽  
Aaron Avivi ◽  
Avner Yayon ◽  
Neal G. Copeland ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptors ◽  
Fibroblast Growth ◽  
Human Chromosomes ◽  
Fibroblast Growth Factor Receptors ◽  
Murine Fibroblast
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