Evidence map›Paper›PMID 20711474›Full record

ArticlePloS one2010

ADAM10 releases a soluble form of the GPNMB/Osteoactivin extracellular domain with angiogenic properties.

April A N Rose, Matthew G Annis, Zhifeng Dong, Francois Pepin, Michael Hallett, Morag Park, Peter M Siegel

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed
4.9field-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

116 citing papers in PubMed, 221 citations in OpenAlex.

  1. Phase I/II study of the antibody-drug conjugate glembatumumab vedotin in patients with advanced melanoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014
    Trial
  2. Article
  3. Plasma proteomics of cerebrovascular disease, cognitive decline, and clinical outcomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  4. A hepatocyte-derived GPNMB-RYK signaling axis in MASH progression.JHEP reports : innovation in hepatology · 2026
    Article
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  8. Trem2 exacerbates ischemic brain injury through Gpnmb in a photothrombotic stroke model.Proceedings of the National Academy of Sciences of the United States of America · 2026
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56 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

7 authors at 3 institutions in 2 countries.

April A N RoseGoodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
Matthew G Annis
Zhifeng Dong
Francois Pepin
Michael Hallett
Morag Park
Peter M Siegel
McGill University · CAMcGill University Health Centre · CALawrence Berkeley National Laboratory · US

Funding

Canadian Institutes of Health Research CTP-79857Canadian Institutes of Health Research MOP-84386
6 · The paper itself

Abstract

backgroundGlycoprotein non-metastatic melanoma protein B (GPNMB)/Osteoactivin (OA) is a transmembrane protein expressed in approximately 40-75% of breast cancers. GPNMB/OA promotes the migration, invasion and metastasis of breast cancer cells; it is commonly expressed in basal/triple-negative breast tumors and is associated with shorter recurrence-free and overall survival times in patients with breast cancer. Thus, GPNMB/OA represents an attractive target for therapeutic intervention in breast cancer; however, little is known about the functions of GPNMB/OA within the primary tumor microenvironment. METHODOLOGY/PRINCIPAL

findingsWe have employed mouse and human breast cancer cells to investigate the effects of GPNMB/OA on tumor growth and angiogenesis. GPNMB/OA-expressing tumors display elevated endothelial recruitment and reduced apoptosis when compared to vector control-derived tumors. Primary human breast cancers characterized by high vascular density also display elevated levels of GPNMB/OA when compared to those with low vascular density. Using immunoblot and ELISA assays, we demonstrate the GPNMB/OA ectodomain is shed from the surface of breast cancer cells. Transient siRNA-mediated knockdown studies of known sheddases identified ADAM10 as the protease responsible for GPNMB/OA processing. Finally, we demonstrate that the shed extracellular domain (ECD) of GPNMB/OA can promote endothelial migration in vitro. CONCLUSIONS/SIGNIFICANCE: GPNMB/OA expression promotes tumor growth, which is associated with enhanced endothelial recruitment. We identify ADAM10 as a sheddase capable of releasing the GPNMB/OA ectodomain from the surface of breast cancer cells, which induces endothelial cell migration. Thus, ectodomain shedding may serve as a novel mechanism by which GPNMB/OA promotes angiogenesis in breast cancer.

Indexed as

ADAM10 ProteinADAM ProteinsAmyloid Precursor Protein SecretasesAnimalsApoptosisBlood VesselsBreast NeoplasmsCell Line, TumorCell MovementEndothelial CellsExtracellular SpaceFemaleGene Expression Regulation, NeoplasticHumansMembrane GlycoproteinsMembrane ProteinsADAM10 ProteinADAM10 protein, humanADAM ProteinsAmyloid Precursor Protein SecretasesGPNMB protein, humanMembrane GlycoproteinsMembrane Proteins

Identifiers

PMID20711474
PMCPMC2919417
OpenAlexW1984065470

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.