| http://purl.uniprot.org/citations/20711474 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20711474 | http://www.w3.org/2000/01/rdf-schema#comment | "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/significanceGPNMB/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."xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0012093"xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://purl.uniprot.org/core/author | "Dong Z."xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://purl.uniprot.org/core/author | "Park M."xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://purl.uniprot.org/core/author | "Siegel P.M."xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://purl.uniprot.org/core/author | "Hallett M."xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://purl.uniprot.org/core/author | "Pepin F."xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://purl.uniprot.org/core/author | "Rose A.A."xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://purl.uniprot.org/core/author | "Annis M.G."xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20711474 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://purl.uniprot.org/core/pages | "e12093"xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://purl.uniprot.org/core/title | "ADAM10 releases a soluble form of the GPNMB/Osteoactivin extracellular domain with angiogenic properties."xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://purl.uniprot.org/core/volume | "5"xsd:string |
| http://purl.uniprot.org/citations/20711474 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20711474 |
| http://purl.uniprot.org/citations/20711474 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/20711474 |
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| http://purl.uniprot.org/uniprot/#_B4DZS5-mappedCitation-20711474 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20711474 |