Evidence map›Paper›PMID 31661464›Full record

ArticleJCI insight2019

EPHB2 carried on small extracellular vesicles induces tumor angiogenesis via activation of ephrin reverse signaling.

Shinya Sato, Suhas Vasaikar, Adel Eskaros, Young Kim, James S Lewis, Bing Zhang, Andries Zijlstra, Alissa M Weaver

Abstract read
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

82 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  10. Dengue Virus NS1 Binds Ephrin B1 to Trigger Endothelial Dysfunction.bioRxiv : the preprint server for biology · 2025
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22 more citing papers are in PubMed but not listed here.

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.

Shinya SatoDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Suhas VasaikarDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Adel EskarosDepartment of Pathology, Microbiology and Immunology, and.
Young KimDepartment of Otolaryngology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
James S LewisDepartment of Pathology, Microbiology and Immunology, and.
Bing ZhangDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Andries ZijlstraDepartment of Pathology, Microbiology and Immunology, and.
Alissa M WeaverDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Funding

VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
iPGDAC, An Integrative Proteogenomic Data Analysis Center for CPTACU24CA210954 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ZHANG, BING · 2016 to 2020
$4.9M
Exosome secretion in breast cancer progressionR01CA206458 · NCI · VANDERBILT UNIVERSITY · PI PONIK, SUZANNE MARIE, WEAVER, ALISSA M · 2016 to 2025
$4.6M
Head & Neck Cancer Neoantigen Characterization & Therapeutic TargetingR01DE027749 · NIDCR · VANDERBILT UNIVERSITY MEDICAL CENTER · PI JOYCE, SEBASTIAN · 2018 to 2022
$2.3M
Cyclic Dinucleotides in Combinatorial Immunotherapy for CancerR01CA178613 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI KIM, YOUNG J. · 2013 to 2017
$1.7M
Exocytic pathways in HNSCC progressionR01CA163592 · NCI · VANDERBILT UNIVERSITY · PI WEAVER, ALISSA M · 2012 to 2016
$1.6M
NCI NIH HHS R01 CA163592NCI NIH HHS R01 CA178613NCI NIH HHS R01 CA206458NCI NIH HHS U24 CA210954NCRR NIH HHS UL1 RR024975NIDCR NIH HHS R01 DE027749
6 · The paper itself

Abstract

Angiogenesis is a key process that allows nutrient uptake and cellular trafficking and is coopted in cancer to enable tumor growth and metastasis. Recently, extracellular vesicles (EVs) have been shown to promote angiogenesis; however, it is unclear what unique features EVs contribute to the process. Here, we studied the role of EVs derived from head and neck squamous cell carcinoma (HNSCC) in driving tumor angiogenesis. Small EVs (SEVs), in the size range of exosomes (50-150 nm), induced angiogenesis both in vitro and in vivo. Proteomic analysis of HNSCC SEVs revealed the cell-to-cell signaling receptor ephrin type B receptor 2 (EPHB2) as a promising candidate cargo to promote angiogenesis. Analysis of patient data further identified EPHB2 overexpression in HNSCC tumors to be associated with poor patient prognosis and tumor angiogenesis, especially in the context of overexpression of the exosome secretion regulator cortactin. Functional experiments revealed that EPHB2 expression in SEVs regulated angiogenesis both in vitro and in vivo and that EPHB2 carried by SEVs stimulates ephrin-B reverse signaling, inducing STAT3 phosphorylation. A STAT3 inhibitor greatly reduced SEV-induced angiogenesis. These data suggest a model in which EVs uniquely promote angiogenesis by transporting Eph transmembrane receptors to nonadjacent endothelial cells to induce ephrin reverse signaling.

Indexed as

AnimalsCell LineEphrinsExosomesExtracellular VesiclesFemaleHumansMiceMice, Inbred C57BLMice, NudeMicroRNAsNeovascularization, PathologicProteomicsReceptor, EphB2Signal TransductionSquamous Cell Carcinoma of Head and NeckEPHB2 protein, humanEphrinsMicroRNAsReceptor, EphB2STAT3 protein, humanSTAT3 Transcription FactorAngiogenesisendothelial cellsHead and neck cancerOncologyProteomics

Identifiers

PMID31661464
PMCPMC6962030

What OpenQuestion holds

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Read underepoch 390

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.