Evidence map›Paper›PMID 29739381›Full record

ArticleBMC cancer2018

Angiopoietin-like 4 promotes osteosarcoma cell proliferation and migration and stimulates osteoclastogenesis.

T Zhang, A Kastrenopoulou, Q Larrouture, N A Athanasou, H J Knowles

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.4field-weighted citation impact, top 4% 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

33 citing papers in PubMed, 47 citations in OpenAlex.

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  13. Research (Washington, D.C.) · 2024
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  14. Primary tumor-derived systemic nANGPTL4 inhibits metastasis.The Journal of experimental medicine · 2023
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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

5 authors at 2 institutions in 2 countries.

T ZhangBotnar Research Centre, Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Headington, Oxford, OX3 7LD, UK.
A KastrenopoulouBotnar Research Centre, Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Headington, Oxford, OX3 7LD, UK.
Q LarroutureBotnar Research Centre, Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Headington, Oxford, OX3 7LD, UK.
N A AthanasouBotnar Research Centre, Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Headington, Oxford, OX3 7LD, UK.
H J KnowlesBotnar Research Centre, Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Headington, Oxford, OX3 7LD, UK. helen.knowles@ndorms.ox.ac.uk.ORCID http://orcid.org/0000-0002-9575-6067
Nuffield Orthopaedic Centre · GBSichuan University · CN

Funding

Arthritis Research UK MP/19200Versus Arthritis 19200
6 · The paper itself

Abstract

backgroundOsteosarcoma is the most common primary bone cancer in children and young adults. It is highly aggressive and patients that present with metastasis have a poor prognosis. Angiopoietin-like 4 (ANGPTL4) drives the progression and metastasis of many solid tumours, but has not been described in osteosarcoma tissue. ANGPTL4 also enhances osteoclast activity, which is required for osteosarcoma growth in bone. We therefore investigated the expression and function of ANGPTL4 in human osteosarcoma tissue and cell lines.

methodsExpression of ANGPTL4 in osteosarcoma tissue microarrays was determined by immunohistochemistry. Hypoxic secretion of ANGPTL4 was tested by ELISA and Western blot. Regulation of ANGPTL4 by hypoxia-inducible factor (HIF) was investigated using isoform specific HIF siRNA (HIF-1α, HIF-2α). Effects of ANGPTL4 on cell proliferation, migration (scratch wound assay), colony formation and osteoblastogenesis were assessed using exogenous ANGPTL4 or cells stably transfected with ANGPTL4. Osteoclastogenic differentiation of CD14+ monocytes was assessed by staining for tartrate-resistant acid phosphatase (TRAP), bone resorption was assessed by lacunar resorption of dentine.

resultsANGPTL4 was immunohistochemically detectable in 76/109 cases. ANGPTL4 was induced by hypoxia in 6 osteosarcoma cell lines, under the control of the HIF-1α transcription factor. MG-63 cells transfected with an ANGPTL4 over-expression plasmid exhibited increased proliferation and migration capacity and promoted osteoclastogenesis and osteoclast-mediated bone resorption. Individually the full-length form of ANGPTL4 could increase MG-63 cell proliferation, whereas N-terminal ANGPTL4 mediated the other pro-tumourigenic phenotypes.

conclusionsThis study describes a role(s) for ANGPTL4 in osteosarcoma and identifies ANGPTL4 as a treatment target that could potentially reduce tumour progression, inhibit angiogenesis, reduce bone destruction and prevent metastatic events.

Indexed as

Gene Expression Regulation, NeoplasticAngiopoietin-Like Protein 4Basic Helix-Loop-Helix ProteinsBone ResorptionCarcinogenesisCell MovementCell ProliferationEndothelial PAS Domain-Containing Protein 1HumansHypoxia-Inducible Factor 1, alpha SubunitNeovascularization, PathologicOsteoclastsOsteogenesisOsteosarcomaRNA, Small InterferingTissue Array AnalysisAngiopoietin-Like Protein 4ANGPTL4 protein, humanBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1HIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitRNA, Small InterferingAngiopoietin-like 4 (ANGPTL4)Bone resoprtionColony formationMigrationOsteoclastogenesisOsteosarcomaProliferation

Identifiers

PMID29739381
PMCPMC5941625
OpenAlexW2806363868

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.