Evidence map›Paper›PMID 25416826›Full record

ArticleNeuro-oncology2015

Development of a Sox2 reporter system modeling cellular heterogeneity in glioma.

Kevin Stoltz, Maksim Sinyuk, James S Hale, Qiulian Wu, Balint Otvos, Kiera Walker, Amit Vasanji, Jeremy N Rich, Anita B Hjelmeland, Justin D Lathia

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

Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

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  17. Mechanistic Parameterization of the Kinomic Signal in Peptide Arrays.Journal of proteomics & bioinformatics · 2016
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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

10 authors at 5 institutions in 1 country.

Kevin StoltzDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (K.S., M.S., J.S.H., B.O., J.D.L.); Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (Q.W., J.N.R.); Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio (M.S., J.D.L.); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama (K.W., A.B.H.); Image I.Q., Cleveland, Ohio (A.V.); Case Comprehensive Cancer Center, Cleveland, Ohio (J.N.R., J.D.L.).
Maksim SinyukDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (K.S., M.S., J.S.H., B.O., J.D.L.); Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (Q.W., J.N.R.); Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio (M.S., J.D.L.); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama (K.W., A.B.H.); Image I.Q., Cleveland, Ohio (A.V.); Case Comprehensive Cancer Center, Cleveland, Ohio (J.N.R., J.D.L.).
James S HaleDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (K.S., M.S., J.S.H., B.O., J.D.L.); Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (Q.W., J.N.R.); Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio (M.S., J.D.L.); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama (K.W., A.B.H.); Image I.Q., Cleveland, Ohio (A.V.); Case Comprehensive Cancer Center, Cleveland, Ohio (J.N.R., J.D.L.).
Qiulian WuDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (K.S., M.S., J.S.H., B.O., J.D.L.); Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (Q.W., J.N.R.); Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio (M.S., J.D.L.); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama (K.W., A.B.H.); Image I.Q., Cleveland, Ohio (A.V.); Case Comprehensive Cancer Center, Cleveland, Ohio (J.N.R., J.D.L.).
Balint OtvosDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (K.S., M.S., J.S.H., B.O., J.D.L.); Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (Q.W., J.N.R.); Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio (M.S., J.D.L.); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama (K.W., A.B.H.); Image I.Q., Cleveland, Ohio (A.V.); Case Comprehensive Cancer Center, Cleveland, Ohio (J.N.R., J.D.L.).
Kiera WalkerDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (K.S., M.S., J.S.H., B.O., J.D.L.); Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (Q.W., J.N.R.); Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio (M.S., J.D.L.); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama (K.W., A.B.H.); Image I.Q., Cleveland, Ohio (A.V.); Case Comprehensive Cancer Center, Cleveland, Ohio (J.N.R., J.D.L.).
Amit VasanjiDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (K.S., M.S., J.S.H., B.O., J.D.L.); Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (Q.W., J.N.R.); Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio (M.S., J.D.L.); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama (K.W., A.B.H.); Image I.Q., Cleveland, Ohio (A.V.); Case Comprehensive Cancer Center, Cleveland, Ohio (J.N.R., J.D.L.).
Jeremy N RichDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (K.S., M.S., J.S.H., B.O., J.D.L.); Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (Q.W., J.N.R.); Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio (M.S., J.D.L.); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama (K.W., A.B.H.); Image I.Q., Cleveland, Ohio (A.V.); Case Comprehensive Cancer Center, Cleveland, Ohio (J.N.R., J.D.L.).
Anita B HjelmelandDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (K.S., M.S., J.S.H., B.O., J.D.L.); Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (Q.W., J.N.R.); Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio (M.S., J.D.L.); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama (K.W., A.B.H.); Image I.Q., Cleveland, Ohio (A.V.); Case Comprehensive Cancer Center, Cleveland, Ohio (J.N.R., J.D.L.).
Justin D LathiaDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (K.S., M.S., J.S.H., B.O., J.D.L.); Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio (Q.W., J.N.R.); Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio (M.S., J.D.L.); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama (K.W., A.B.H.); Image I.Q., Cleveland, Ohio (A.V.); Case Comprehensive Cancer Center, Cleveland, Ohio (J.N.R., J.D.L.).
Cleveland Clinic Lerner College of Medicine · USCleveland Foundation · USCleveland State University · USCase Comprehensive Cancer CenterCleveland Clinic · US

Funding

Vaccine Immunotoxin and Radioimmunotherapy of Primary and Metastatic CNS TumorsP01CA154291 · NCI · DUKE UNIVERSITY · PI BIGNER, DARELL D · 2012 to 2016
$14.5M
Novel adhesion mechanisms in glioblastoma stem cellsR01NS083629 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI LATHIA, JUSTIN D. · 2013 to 2017
$1.7M
A20 Promotes Glioma Stem Cell Mediated TumorigenesisR01CA151522 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI HJELMELAND, ANITA BORTON · 2010 to 2014
$1.2M
Microenvironmental regulation of the cancer stem cell phenotype by integrin a6R00CA157948 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LATHIA, JUSTIN D. · 2012 to 2014
$725k
3D-Microtumor_GBM Xenoline Proband Modeling of Kinome-Directed TherapyR21CA185712 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI WILLEY, CHRISTOPHER D · 2014 to 2015
$363k
Microenvironmental modulation as a result of glioma therapyK99CA157948 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LATHIA, JUSTIN D. · 2011 to 2011
$99k
NCI NIH HHS K99 CA157948NCI NIH HHS K99/R00 CA157948NCI NIH HHS P01 CA154291NCI NIH HHS R00 CA157948NCI NIH HHS R01CA1515122NCI NIH HHS R01 CA151522NCI NIH HHS R21 CA185712NINDS NIH HHS R01 NS083629
6 · The paper itself

Abstract

backgroundMalignant gliomas are complex systems containing a number of factors that drive tumor initiation and progression, including genetic aberrations that lead to extensive cellular heterogeneity within the neoplastic compartment. Mouse models recapitulate these genetic aberrations, but readily observable heterogeneity remains challenging.

methodsTo interrogate cellular heterogeneity in mouse glioma models, we utilized a replication-competent avian sarcoma-leukosis virus long terminal repeat with splice acceptor/tumor virus A (RCAS-tva) system to generate spontaneous mouse gliomas that contained a Sox2-enhanced green fluorescent protein (EGFP) reporter. Glial fibrillary acidic protein-tva mice were crossed with Sox2-EGFP mice, and tumors were initiated that contained a subpopulation of Sox2-EGFP-high cells enriched for tumor-initiating cell properties such as self-renewal, multilineage differentiation potential, and perivascular localization.

resultsFollowing implantation into recipient mice, Sox2-EGFP-high cells generated tumors containing Sox2-EGFP-high and Sox2-EGFP-low cells. Kinomic analysis of Sox2-EGFP-high cells revealed activation of known glioma signaling pathways that are strongly correlated with patient survival including platelet-derived growth factor receptor beta, phosphoinositide-3 kinase, and vascular endothelial growth factor. Our functional analysis identified active feline sarcoma (Fes) signaling in Sox2-EGFP-high cells. Fes negatively correlated with glioma patient survival and was coexpressed with Sox2-positive cells in glioma xenografts and primary patient-derived tissue.

conclusionsOur RCAS-tva/Sox2-EGFP model will empower closer examination of cellular heterogeneity and will be useful for identifying novel glioma pathways as well as testing preclinical treatment efficacy.

Indexed as

Disease Models, AnimalGenes, ReporterAnimalsAvian Leukosis VirusAvian Sarcoma VirusesBrain NeoplasmsGenetic VectorsGliomaGreen Fluorescent ProteinsHumansMiceMice, TransgenicNeoplastic Stem CellsSignal TransductionSOXB1 Transcription FactorsTumor Cells, Culturedenhanced green fluorescent proteinGreen Fluorescent ProteinsSOX2 protein, humanSOXB1 Transcription Factorsgliomaintratumoral heterogeneityRCAS/tvaSox2

Identifiers

PMID25416826
PMCPMC4483103
OpenAlexW2062031080

What Socratic holds

Textmetadata
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 Socratic graph.