Evidence map›Paper›PMID 27009237›Full record

ArticleNeuro-oncology2016

Autocrine VEGFR1 and VEGFR2 signaling promotes survival in human glioblastoma models in vitro and in vivo.

Emese Szabo, Hannah Schneider, Katharina Seystahl, Elisabeth Jane Rushing, Frank Herting, K Michael Weidner, Michael Weller

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 80 citations in OpenAlex.

  1. Trial
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  7. Article
  8. Cell and gene therapy in neuro-oncology.Handbook of clinical neurology · 2024
    Review
  9. Review
  10. Review
  11. VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway.Signal transduction and targeted therapy · 2023
    Article
  12. Review
  13. Review
  14. Article
  15. Gene Therapy for High Grade Glioma: The Clinical Experience.Expert opinion on biological therapy · 2023
    Review
  16. Signaling pathways in brain tumors and therapeutic interventions.Signal transduction and targeted therapy · 2023
    Review
  17. Article
  18. Article
  19. Molecular and Circulating Biomarkers in Patients with Glioblastoma.International journal of molecular sciences · 2022
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Emese SzaboLaboratory of Molecular Neuro-Oncology, Department of Neurology (E.S., H.S., K.S., M.W.), and Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland (E.J.R); Roche Innovation Center Penzberg, Roche Pharma Research and Early Development, Nonnenwald 2, Penzberg D-82372, Germany (F.H., K.M.W.).
Hannah SchneiderLaboratory of Molecular Neuro-Oncology, Department of Neurology (E.S., H.S., K.S., M.W.), and Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland (E.J.R); Roche Innovation Center Penzberg, Roche Pharma Research and Early Development, Nonnenwald 2, Penzberg D-82372, Germany (F.H., K.M.W.).
Katharina SeystahlLaboratory of Molecular Neuro-Oncology, Department of Neurology (E.S., H.S., K.S., M.W.), and Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland (E.J.R); Roche Innovation Center Penzberg, Roche Pharma Research and Early Development, Nonnenwald 2, Penzberg D-82372, Germany (F.H., K.M.W.).
Elisabeth Jane RushingLaboratory of Molecular Neuro-Oncology, Department of Neurology (E.S., H.S., K.S., M.W.), and Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland (E.J.R); Roche Innovation Center Penzberg, Roche Pharma Research and Early Development, Nonnenwald 2, Penzberg D-82372, Germany (F.H., K.M.W.).
Frank HertingLaboratory of Molecular Neuro-Oncology, Department of Neurology (E.S., H.S., K.S., M.W.), and Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland (E.J.R); Roche Innovation Center Penzberg, Roche Pharma Research and Early Development, Nonnenwald 2, Penzberg D-82372, Germany (F.H., K.M.W.).
K Michael WeidnerLaboratory of Molecular Neuro-Oncology, Department of Neurology (E.S., H.S., K.S., M.W.), and Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland (E.J.R); Roche Innovation Center Penzberg, Roche Pharma Research and Early Development, Nonnenwald 2, Penzberg D-82372, Germany (F.H., K.M.W.).
Michael WellerLaboratory of Molecular Neuro-Oncology, Department of Neurology (E.S., H.S., K.S., M.W.), and Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland (E.J.R); Roche Innovation Center Penzberg, Roche Pharma Research and Early Development, Nonnenwald 2, Penzberg D-82372, Germany (F.H., K.M.W.) michael.weller@usz.ch.
Roche Pharma AG (Germany) · DERoche (Switzerland) · CHUniversity Hospital of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlthough the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) system has become a prime target for antiangiogenic treatment, its biological role in glioblastoma beyond angiogenesis has remained controversial.

methodsUsing neutralizing antibodies to VEGF or placental growth factor (PlGF) or the tyrosine kinase inhibitor, cediranib, or lentiviral gene silencing, we delineated autocrine signaling in glioma cell lines. The in vivo effects of VEGFR1 and VEGFR2 depletion were evaluated in orthotopic glioma xenograft models.

resultsVEGFR1 and VEGFR2 modulated glioma cell clonogenicity, viability, and invasiveness in vitro in an autocrine, cell-line-specific manner. VEGFR1 silencing promoted mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling, whereas VEGFR2 silencing resulted in cell-type dependent activation of the protein kinase B (PKB)/AKT and MAPK/ERK pathways. These responses may represent specific escape mechanisms from VEGFR inhibition. The survival of orthotopic glioma-bearing mice was prolonged upon VEGFR1 silencing in the LNT-229, LN-308, and U87MG models and upon VEGFR2 silencing in LN-308 and U87MG. Disruption of VEGFR1 and VEGFR2 signaling was associated with decreased tumor size, increased tumor necrosis, or loss of matrix metalloproteinase 9 (MMP9) immunoreactivity. Neutralizing VEGF and PlGF by specific antibodies was superior to either antibody treatment alone in the VEGFR1-dependent LNT-229 model.

conclusionsDifferential dependence on autocrine signaling through VEGFR1 and VEGFR2 suggests a need for biomarker-stratified VEGF(R)-based therapeutic approaches to glioblastoma.

Indexed as

Autocrine CommunicationCell ProliferationAnimalsApoptosisExtracellular Signal-Regulated MAP KinasesFemaleGlioblastomaHumansIn Vitro TechniquesMiceMice, NudeNeovascularization, PathologicSignal TransductionTumor Cells, CulturedVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2Extracellular Signal-Regulated MAP KinasesVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2angiogenesisglioblastomaPlGFsignalingVEGF

Identifiers

PMID27009237
PMCPMC4998998
OpenAlexW2304044561

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.