Non-invasive neural stem cells become invasive in vitro by combinatorial FGF2 and BMP4 signaling

Sailer, Martin; Gerber, Alexandra Lehmkuhl; Tostado, Cristobal; Hütter, Gregor; Cordier, Dominik; Mariani, Luigi; Ritz, Marie‐Françoise

doi:10.1242/jcs.125757

Cited by 24 publications

(17 citation statements)

References 56 publications

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“…FGF-1 induced fibroblast invasion, but not migration, whereas PDGF-AB and thrombin induced fibroblast migration, but not invasion. Of the mediators we found to induce invasion of primary mouse lung fibroblasts, PDGF-BB, EGF, and FGF-1 have been previously noted to induce invasion of fibroblasts isolated from other sources (32,(36)(37)(38), and LPA, FGF-1, and FGF-2 have been previously noted to induce cancer cell invasion (38)(39)(40)(41). Consistent with our finding that these mediators are able to induce fibroblast invasion ex vivo, we found evidence to suggest that these mediators all contribute to the non-cell-autonomous fibroblast invasion induced in vivo in the bleomycin model: knockdown of lung fibroblast PDGFRb, LPA 1 , EGFR, or FGFR2 expression each, by themselves, significantly decreased fibroblast invasion induced by BAL from bleomycin-challenged mice.…”

Section: Discussionmentioning

confidence: 75%

Fibrogenic Lung Injury Induces Non–Cell-Autonomous Fibroblast Invasion

Ahluwalia

Grasberger

Mugo

et al. 2016

Am J Respir Cell Mol Biol

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Pathologic accumulation of fibroblasts in pulmonary fibrosis appears to depend on their invasion through basement membranes and extracellular matrices. Fibroblasts from the fibrotic lungs of patients with idiopathic pulmonary fibrosis (IPF) have been demonstrated to acquire a phenotype characterized by increased cell-autonomous invasion. Here, we investigated whether fibroblast invasion is further stimulated by soluble mediators induced by lung injury. We found that bronchoalveolar lavage fluids from bleomycin-challenged mice or patients with IPF contain mediators that dramatically increase the matrix invasion of primary lung fibroblasts. Further characterization of this non-cell-autonomous fibroblast invasion suggested that the mediators driving this process are produced locally after lung injury and are preferentially produced by fibrogenic (e.g., bleomycin-induced) rather than nonfibrogenic (e.g., LPS-induced) lung injury. Comparison of invasion and migration induced by a series of fibroblast-active mediators indicated that these two forms of fibroblast movement are directed by distinct sets of stimuli. Finally, knockdown of multiple different membrane receptors, including platelet-derived growth factor receptor-b, lysophosphatidic acid 1, epidermal growth factor receptor, and fibroblast growth factor receptor 2, mitigated the non-cell-autonomous fibroblast invasion induced by bronchoalveolar lavage from bleomycin-injured mice, suggesting that multiple different mediators drive fibroblast invasion in pulmonary fibrosis. The magnitude of this mediator-driven fibroblast invasion suggests that its inhibition could be a novel therapeutic strategy for pulmonary fibrosis. Further elaboration of the molecular mechanisms that drive non-cell-autonomous fibroblast invasion consequently may provide a rich set of novel drug targets for the treatment of IPF and other fibrotic lung diseases.Keywords: idiopathic pulmonary fibrosis; pathogenesis; fibroblast; invasion; migration Idiopathic pulmonary fibrosis (IPF) is a disease of great unmet medical need. Aberrant or overexuberant wound healing responses to chronic lung injury are now thought to be responsible for the excessive fibroblast accumulation and extracellular matrix deposition that distort the lung's architecture and compromise its function in IPF (1, 2). Better characterization of these abnormal responses to lung injury should provide a rich set of therapeutic targets for novel IPF therapies.The abnormal accumulation of fibroblasts is a central hallmark of fibrotic tissues, including the lung in IPF. In addition to fibroblast proliferation, fibroblast accumulation in pulmonary fibrosis appears to fundamentally depend on: (1) the migration of these cells to sites of tissue injury; and (2) their ability to invade extracellular matrix. Although migration

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Section: Discussionmentioning

confidence: 75%

Fibrogenic Lung Injury Induces Non–Cell-Autonomous Fibroblast Invasion

Ahluwalia

Grasberger

Mugo

et al. 2016

Am J Respir Cell Mol Biol

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“…In gliomas, IGFBP2 is considered to be an oncogene that causes glioma progression through integrin/ILK/NF-kB pathway (Phillips et al, 2016). According to reports, Podoplanin (PDPN) was a novel candidate gene that might play an essential role in glioblastoma pathogenesis and response to treatment (Sailer et al, 2013;Krishnan et al, 2018). However, these genes and the related signaling pathways and mechanisms involved are still not clear enough.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis to Evaluate the Prognostic Value of Signature mRNAs in Glioblastoma Multiforme

Yang

Wang

et al. 2020

Front. Genet.

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Background: Gliomas are the most common intracranial tumors and are classified as I-IV. Among them, glioblastoma multiforme (GBM) is the most common invasive glioma with a poor prognosis. New molecular biomarkers that can predict clinical outcomes in GBM patients must be identified, which will help comprehend their pathogenesis and supply personalized treatment. Our research revealed four powerful survival indicators in GBM by reanalyzing microarray data and genetic sequencing data in public databases. Moreover, it unraveled new potential therapeutic targets which could help improve the survival time and quality of life of GBM patients. Materials and Methods: To identify prognostic signatures in GBMs, we analyzed the gene profiling data of GBM and standard brain samples from the Gene Expression Omnibus, including four datasets and RNA sequencing data from The Cancer Genome Atlas (TCGA) containing 152 glioblastoma tissues. We performed the differential analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, weighted gene co-expression network analysis (WGCNA) and Cox regression analysis. Results: After differential analysis in GSE12657, GSE15824, GSE42656 and GSE50161, overlapping differentially expressed genes were identified. We identified 110 up-regulated DEGs and 75 down-regulated DEGs in the GBM samples. Significantly enriched subclasses of the GO classification of these genes included mitotic sister chromatid separation, mitotic nuclear division and so on. In KEGG pathway analysis, the most abundant terms were ECM-receptor interaction and protein digestion and absorption. WGCNA analysis was performed on these 185 DEGs in 152 glioblastoma samples obtained from TCGA, and gene co-expression networks were constructed. We then performed a multivariate Cox analysis and established a Cox proportional hazards regression model using the top 20 genes significantly correlated with survival time. We

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“…Witty et al (2014) have reported the presence of podoplanin as a marker of epicardial lineage cells generated from human pluripotent stem cells by stage-specific activation of the BMP and Wnt signaling pathway. Sailer et al (2013) have studied the properties of rat neural stem cells, normally non-invasive. However, in the presence of FGF2 and BMP4 they acquire a migratory and invasive phenotype.…”

Section: In Vivo Studiesmentioning

confidence: 99%