Evidence map›Paper›PMID 25745997›Full record

ArticleOncogene2015

Blocking CLEC14A-MMRN2 binding inhibits sprouting angiogenesis and tumour growth.

P J Noy, P Lodhia, K Khan, X Zhuang, D G Ward, A R Verissimo, A Bacon, R Bicknell

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

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 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 1 institution in 1 country.

P J NoyAngiogenesis Laboratory, Institute for Biomedical Research, Schools of Immunity and Infection and Cancer Sciences, College of Medical and Dental Sciences, The Medical School, University of Birmingham, Birmingham, UK.
P LodhiaAngiogenesis Laboratory, Institute for Biomedical Research, Schools of Immunity and Infection and Cancer Sciences, College of Medical and Dental Sciences, The Medical School, University of Birmingham, Birmingham, UK.
K KhanAngiogenesis Laboratory, Institute for Biomedical Research, Schools of Immunity and Infection and Cancer Sciences, College of Medical and Dental Sciences, The Medical School, University of Birmingham, Birmingham, UK.
X ZhuangAngiogenesis Laboratory, Institute for Biomedical Research, Schools of Immunity and Infection and Cancer Sciences, College of Medical and Dental Sciences, The Medical School, University of Birmingham, Birmingham, UK.
D G WardInstitute of Cancer Studies, School of Cancer Sciencies, University of Birmingham, Birmingham, UK.
A R VerissimoAngiogenesis Laboratory, Institute for Biomedical Research, Schools of Immunity and Infection and Cancer Sciences, College of Medical and Dental Sciences, The Medical School, University of Birmingham, Birmingham, UK.
A BaconSchool of Immunity and Infection, Institute for Biomedical Research, The Medical School, University of Birmingham, Birmingham, UK.
R BicknellAngiogenesis Laboratory, Institute for Biomedical Research, Schools of Immunity and Infection and Cancer Sciences, College of Medical and Dental Sciences, The Medical School, University of Birmingham, Birmingham, UK.
University of Birmingham · GB

Funding

Cancer Research UK A13027Cancer Research UK C4719/A6766Medical Research Council
6 · The paper itself

Abstract

We previously identified CLEC14A as a tumour endothelial marker. Here we show that CLEC14A is a regulator of sprouting angiogenesis in vitro and in vivo. Using a human umbilical vein endothelial cell spheroid-sprouting assay, we found CLEC14A to be a regulator of sprout initiation. Analysis of endothelial sprouting in aortic ring and in vivo subcutaneous sponge assays from clec14a(+/+) and clec14a(-/-) mice revealed defects in sprouting angiogenesis in CLEC14A-deficient animals. Tumour growth was retarded and vascularity reduced in clec14a(-/-) mice. Pull-down and co-immunoprecipitation experiments confirmed that MMRN2 binds to the extracellular region of CLEC14A. The CLEC14A-MMRN2 interaction was interrogated using mouse monoclonal antibodies. Monoclonal antibodies were screened for their ability to block this interaction. Clone C4, but not C2, blocked CLEC14A-MMRN2 binding. C4 antibody perturbed tube formation and endothelial sprouting in vitro and in vivo, with a similar phenotype to loss of CLEC14A. Significantly, tumour growth was impaired in C4-treated animals and vascular density was also reduced in the C4-treated group. We conclude that CLEC14A-MMRN2 binding has a role in inducing sprouting angiogenesis during tumour growth, which has the potential to be manipulated in future antiangiogenic therapy design.

Indexed as

AnimalsAntibodies, MonoclonalAntigens, SurfaceAortaCell Adhesion MoleculesCoculture TechniquesGene Knockdown TechniquesHumansHuman Umbilical Vein Endothelial CellsLectins, C-TypeMembrane GlycoproteinsMiceNeovascularization, PathologicProtein BindingRNA, Small InterferingSpheroids, CellularAntibodies, MonoclonalAntigens, SurfaceCell Adhesion MoleculesCLEC14A protein, humanEMILIN3 protein, humanLectins, C-TypeMembrane GlycoproteinsRNA, Small Interfering

Identifiers

PMID25745997
PMCPMC4724939
OpenAlexW2041291777

What OpenQuestion holds

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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.