Evidence map›Paper›PMID 21618524›Full record

ArticleInternational journal of cancer2012

IGF binding protein-6 expression in vascular endothelial cells is induced by hypoxia and plays a negative role in tumor angiogenesis.

Chunyang Zhang, Ling Lu, Yun Li, Xianlei Wang, Jianfeng Zhou, Yunzhang Liu, Ping Fu, Marisa A Gallicchio, Leon A Bach, Cunming Duan

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

Article in International journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.3field-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

32 citing papers in PubMed, 63 citations in OpenAlex.

  1. Review
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  10. IGFBP-6: At the Crossroads of Immunity, Tissue Repair and Fibrosis.International journal of molecular sciences · 2022
    Review
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  20. Genome-wide analysis identifies differential promoter methylation of Leprel2, Foxf1, Mmp25, Igfbp6, and Peg12 in murine tendinopathy.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2017
    Article
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 3 institutions in 3 countries.

Chunyang ZhangKey Laboratory of Marine Drugs (Ocean University of China), Ministry of Education and School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, China.
Ling Lu
Yun Li
Xianlei Wang
Jianfeng Zhou
Yunzhang Liu
Ping Fu
Marisa A Gallicchio
Leon A Bach
Cunming Duan
Ocean University of China · CNMonash University · AUUniversity of Michigan–Ann Arbor · US

Funding

IGF-I AND PROTEINS IN VASCULAR SMOOTH MUSCLE CELLSR01HL060679 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DUAN, CUNMING · 2000 to 2008
$2.0M
NHLBI NIH HHS 2R01HL60679NHLBI NIH HHS R01 HL060679
6 · The paper itself

Abstract

Hypoxia stimulates tumor angiogenesis by inducing the expression of angiogenic molecules. The negative regulators of this process, however, are not well understood. Here, we report that hypoxia induced the expression of insulin-like growth factor binding protein-6 (IGFBP-6), a tumor repressor, in human and rodent vascular endothelial cells (VECs) via a hypoxia-inducible factor (HIF)-mediated mechanism. Addition of human IGFBP-6 to cultured human VECs inhibited angiogenesis in vitro. An IGFBP-6 mutant with at least 10,000-fold lower binding affinity for IGFs was an equally potent inhibitor of angiogenesis, suggesting that this action of IGFBP-6 is IGF-independent. The functional relationship between IGFBP-6 and vascular endothelial growth factor (VEGF), a major hypoxia-inducible angiogenic molecule, was examined. While VEGF alone increased angiogenesis in vitro, co-incubation with IGFBP-6 abolished VEGF-stimulated angiogenesis. The in vivo role of IGFBP-6 in angiogenesis was tested in flk1:GFP zebrafish embryos, which exhibit green fluorescence protein in developing vascular endothelium, permitting visualization of developing blood vessels. Injection of human IGFBP-6 mRNA reduced the number of embryonic inter-segmental blood vessels by ∼40%. This anti-angiogenic activity is conserved in zebrafish because expression of zebrafish IGFBP-6b had similar effects. To determine the anti-angiogenic effect of IGFBP-6 in a tumor model, human Rh30 rhabdomyosarcoma cells stably transfected with IGFBP-6 were inoculated into athymic BALB/c nude mice. Vessel density was 52% lower in IGFBP-6-transfected xenografts than in vector control xenografts. These results suggest that the expression of IGFBP-6 in VECs is up-regulated by hypoxia and IGFBP-6 inhibits angiogenesis in vitro and in vivo.

Indexed as

AnimalsCell HypoxiaCell Line, TumorEndothelial CellsFemaleHumansHuman Umbilical Vein Endothelial CellsHypoxia-Inducible Factor 1Insulin-Like Growth Factor Binding Protein 6Insulin-Like Growth Factor IMiceMice, NudeNeovascularization, PathologicRatsRhabdomyosarcomaVascular Endothelial Growth Factor AHypoxia-Inducible Factor 1Insulin-Like Growth Factor Binding Protein 6Insulin-Like Growth Factor IVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID21618524
PMCPMC3259243
OpenAlexW2095649324

What OpenQuestion holds

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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.