Evidence map›Paper›PMID 27125842›Full record

ArticleThe Journal of pathology2016

Glioma progression is mediated by an addiction to aberrant IGFBP2 expression and can be blocked using anti-IGFBP2 strategies.

Lynette M Phillips, Xinhui Zhou, David E Cogdell, Corrine Yingxuan Chua, Anouk Huisinga, Kenneth R Hess, Gregory N Fuller, Wei Zhang

Open access · greenAbstract read
In one paragraph

Article in The Journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

35 citing papers in PubMed, 50 citations in OpenAlex.

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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

8 authors at 3 institutions in 3 countries.

Lynette M PhillipsDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Xinhui ZhouDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
David E CogdellDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Corrine Yingxuan ChuaDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Anouk HuisingaDepartment of Pathology, Radboud University Nijmegen Medical Centre, 6500, Nijmegen, The Netherlands.
Kenneth R HessDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Gregory N FullerDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Wei ZhangDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
The University of Texas MD Anderson Cancer Center · USCenter for Genomic Science · ITRadboud University Medical Center · NL

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Center for Systems Analysis of the Cancer RegulomeU24CA143835 · NCI · INSTITUTE FOR SYSTEMS BIOLOGY · PI SHMULEVICH, ILYA · 2009 to 2016
$10.6M
glioma Through Genomics and Transgenic Mouse ModelR01CA098503 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI FULLER, GREGORY NEAL, ZHANG, WEI · 2004 to 2014
$2.2M
Oncogene cooperation in glioma genesisR01CA141432 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FULLER, GREGORY NEAL, ZHANG, WEI · 2010 to 2014
$1.6M
Dissecting Glioma Genesis through a Glial-Specific Mouse ModelR56CA098503 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FULLER, GREGORY NEAL, ZHANG, WEI · 2009 to 2009
$247k
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA098503NCI NIH HHS R01 CA141432NCI NIH HHS R56 CA098503NCI NIH HHS U24 CA143835
6 · The paper itself

Abstract

Insulin-like growth factor binding protein 2 (IGFBP2) overexpression is common in high-grade glioma and is both a strong biomarker of aggressive behaviour and a well-documented prognostic factor. IGFBP2 is a member of the secreted IGFBP family that functions by interacting with circulating IGFs to modulate IGF-mediated signalling. This traditional view of IGFBP2 activities has been challenged by the recognition of the diverse functions and cellular locations of members of the IGFBP family. IGFBP2 has been previously established as a driver of glioma progression to a higher grade. In this study, we sought to determine whether IGFBP2-overexpressing tumours are dependent on continued oncogene expression and whether IGFBP2 is a viable therapeutic target in glioma. We took advantage of the well-characterized RCAS/Ntv-a mouse model to create a doxycycline-inducible IGFBP2 model of glioma and demonstrated that the temporal expression of IGFBP2 has dramatic impacts on tumour progression and survival. Further, we demonstrated that IGFBP2-driven tumours are dependent on the continued expression of IGFBP2, as withdrawal of this oncogenic signal led to a significant decrease in tumour progression and prolonged survival. Inhibition of IGFBP2 also impaired tumour cell spread. To assess a therapeutically relevant inhibition strategy, we evaluated a neutralizing antibody against IGFBP2 and demonstrated that it impaired downstream IGFBP2-mediated oncogenic signalling pathways. The studies presented here indicate that IGFBP2 not only is a driver of glioma progression and a prognostic factor but is also required for tumour maintenance and thus represents a viable therapeutic target in the treatment of glioma. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsAnimals, NewbornAntibodies, NeutralizingBrain NeoplasmsCell Line, TumorDisease Models, AnimalDisease ProgressionDoxycyclineGliomaHumansInsulin-Like Growth Factor Binding Protein 2MiceOncogenesPrognosisSignal TransductionAntibodies, NeutralizingDoxycyclineInsulin-Like Growth Factor Binding Protein 2gliomaIGFBP2RCAS mouse model

Identifiers

PMID27125842
PMCPMC4915980
OpenAlexW2345210474

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

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.