FGF5 as an oncogenic factor in human glioblastoma multiforme: autocrine and paracrine activities

Allerstorfer, Sigrid; Sonvilla, Gudrun; Fischer, Hendrik; Spiegl-Kreinecker, Sabine; Gauglhofer, Christine; Setinek, Ulrike; Czech, Thomas; Marosi, Christine; Buchroithner, Johanna; Pichler, Josef; Silye, René; Mohr, Thomas; Holzmann, Klaus; Grasl‐Kraupp, Bettina; Marian, Brigitte; Grusch, Michael; Fischer, Johannes; Micksche, M.; Berger, Walter

doi:10.1038/onc.2008.61

Cited by 88 publications

(78 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our observations of an essential requirement for FGF signaling in astrocyte development in vivo in Drosophila suggests that a detailed analysis of FGF signaling pathways in mammalian astrocyte development should prove fruitful. FGF signaling is known to be perturbed in glioma (Allerstorfer et al, 2008; Mohanan et al, 2012; Yamada et al, 2002) and our observations of the key role for FGFs in astrocyte process outgrowth may ultimately provide insight into the highly invasive nature of glioma cells in the brain.…”

Section: Discussionmentioning

confidence: 68%

Neuron-Glia Interactions through the Heartless FGF Receptor Signaling Pathway Mediate Morphogenesis of Drosophila Astrocytes

Stork

Sheehan

Tasdemir-Yilmaz

et al. 2014

Neuron

203

296

View full text Add to dashboard Cite

Summary Astrocytes are critically important for neural circuit assembly and function. Mammalian protoplasmic astrocytes develop a dense ramified meshwork of cellular processes to form intimate contacts with neuronal cell bodies, neurites and synapses. This close neuron-glia morphological relationship is essential for astrocyte function, but it remains unclear how astrocytes establish their intricate morphology, organize spatial domains, and associate with neurons and synapses in vivo. Here we characterize a Drosophila glial subtype that shows striking morphological and functional similarities to mammalian astrocytes. We demonstrate the Fibroblast growth factor (FGF) receptor Heartless autonomously controls astrocyte membrane growth, and the FGFs Pyramus and Thisbe direct astrocyte processes to ramify specifically in CNS synaptic regions. We further show the shape and size of individual astrocytes are dynamically sculpted through inhibitory or competitive astrocyte-astrocyte interactions and Heartless FGF signaling. Our data identify FGF signaling through Heartless as a key regulator of astrocyte morphological elaboration in vivo.

show abstract

Section: Discussionmentioning

confidence: 68%

Neuron-Glia Interactions through the Heartless FGF Receptor Signaling Pathway Mediate Morphogenesis of Drosophila Astrocytes

Stork

Sheehan

Tasdemir-Yilmaz

et al. 2014

Neuron

203

296

View full text Add to dashboard Cite

show abstract

“…The role of FGF5 in regulating endothelial cell function is less well characterized, although it is overexpressed in human glioblastoma and promotes malignant progression through FGFR1-dependent signaling (Allerstorfer et al, 2008). Based on these functions, we focused on characterizing the role of FGFR1 signaling in regulating crosstalk between basal cells and endothelial cells.…”

Section: Resultsmentioning

confidence: 99%

Endothelial MMP14 is required for endothelial dependent growth support of human airway basal cells

Ding

Gomi

Rafii

et al. 2015

Journal of Cell Science

View full text Add to dashboard Cite

Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying nonepithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated signaling. Building on these findings, we found, by RNA sequencing analysis, that basal cells expressed multiple fibroblast growth factor (FGF) ligands (FGF2, FGF5, FGF11 and FGF13) and that only FGF2 and FGF5 were capable of functioning in a paracrine manner to activate classical FGF receptor (FGFR) signaling. Antibody-mediated blocking of FGFR1 during basal-cell-endothelialcell co-culture significantly reduced the endothelial-cell-dependent basal cell growth. Stimulation of endothelial cells with basal-cell-derived growth factors induced endothelial cell expression of matrix metallopeptidase 14 (MMP14), and short hairpin RNA (shRNA)-mediated knockdown of endothelial cell MMP14 significantly reduced the endothelial-cell-dependent growth of basal cells. Overall, these data characterize a new growth-factor-mediated reciprocal 'crosstalk' between human airway basal cells and endothelial cells that regulates proliferation of basal cells.

show abstract

“…19 Our recent studies demonstrate that many bladder tumors also express high levels of FGFR1. 18 Increased expression of FGFR1 has been observed in numerous cancer types including breast, 25 prostate, 26 glioblastoma, 27,28 and astrocytoma. 29 In our previous study, no relationship of total FGFR1 mRNA and tumor stage or grade was observed in UC.…”

Section: Discussionmentioning

confidence: 99%

Altered Splicing of FGFR1 Is Associated with High Tumor Grade and Stage and Leads to Increased Sensitivity to FGF1 in Bladder Cancer

Tomlinson

Knowles

2010

The American Journal of Pathology

View full text Add to dashboard Cite

Fibroblast growth factor receptors (FGFRs) play key roles in proliferation, differentiation, and tumorigenesis. Previously, we demonstrated that FGFR1 expression is increased in urothelial carcinoma cell lines and tumors, which promotes proliferation and survival via activation of the mitogen-activated protein kinase (MAPK) pathway. Here we examined splice variants of FGFR1 in both urothelial carcinoma cell lines and tumors. Two known FGFR1 IIIc splice variants (FGFR1␣ and FGFR1␤) were expressed. FGFR1␤ lacks exon 3 of FGFR1␣, removing the first Ig loop of the extracellular domain. Both isoforms were expressed at similar levels in normal urothelial cells, but FGFR1␤ was expressed at higher levels in most tumor cell lines. In tumor tissues, expression levels were higher than in controls, and the FGFR1␤: FGFR1␣ ratio was significantly increased in association with tumor stage and grade. When FGFR1␣ and FGFR1␤ were expressed in urothelial cells, no differences in signaling were observed. FGFR1-induced proliferation paralleled MAPK pathway activation. The relative activation of FGFR1␤ and FGFR1␣ by all known mammalian FGFs was examined. Both isoforms were activated by the same FGFs, but the level of activation differed. FGFR1␤ showed higher affinity for low concentrations of FGF1, leading to enhanced signaling and increased proliferation. An FGFR1␣-to-FGFR1␤ isoform switch and increased FGF1-induced activation of FGFR1␤ may result in a proliferative advantage that plays a key role during bladder tumor progression.

show abstract

FGF5 as an oncogenic factor in human glioblastoma multiforme: autocrine and paracrine activities

Cited by 88 publications

References 45 publications

Neuron-Glia Interactions through the Heartless FGF Receptor Signaling Pathway Mediate Morphogenesis of Drosophila Astrocytes

Neuron-Glia Interactions through the Heartless FGF Receptor Signaling Pathway Mediate Morphogenesis of Drosophila Astrocytes

Endothelial MMP14 is required for endothelial dependent growth support of human airway basal cells

Altered Splicing of FGFR1 Is Associated with High Tumor Grade and Stage and Leads to Increased Sensitivity to FGF1 in Bladder Cancer

Contact Info

Product

Resources

About