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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2003-4-17
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pubmed:abstractText |
The Ewing's sarcoma family of tumors (ESFT) contain a translocation, t(11;22), which results in the novel oncogenic fusion protein EWS/FLI1. Platelet-derived growth factors (PDGF) and their receptors (PDGFR) are involved in the induction and proliferation of numerous solid tumors and are the potential candidates for novel targeted antitumor therapy. Since a relation was reported between PDGF-C and EWS/FLI1, we sought to characterize the PDGF signaling pathway in ESFT. Eight out of nine ESFT cell lines were found to express significant levels of beta-PDGFR. Interestingly, none of the tested cell lines expressed alpha-PDGFR, which is the receptor isotype required for PDGF-C binding. By immunohistochemical staining 47 of 52 (90.4%) archival tumor samples from patients with ESFT were positive for beta-PDGFR. ESFT cell lines were treated with PDGF-AA or PDGF-BB ligands to evaluate downstream signaling. Autophosphorylation of beta-PDGFR and tyrosine phosphorylation of PLC-gamma, PI3Kp85 and Shc were detected only in PDGF-BB-stimulated cells that express beta-PDGFR. Receptor function was further evaluated using chemotaxis assays that showed TC-32 cell migration towards PDGF-BB. A specific PDGFR kinase inhibitor AG1295 blocked beta-PDGFR activation, downstream signaling, growth in cell culture and chemotaxis of TC-32 cells. AG1295 also delayed tumor formation and prolonged survival in an ESFT animal model. We conclude that ESFT express beta-PDGFR and that this is a functional and potentially crucial signaling pathway. Therefore, beta-PDGFRs may provide a novel therapeutic target in ESFT that can be utilized to design better treatment modalities.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/6,7-dimethoxy-2-phenylquinoxaline,
http://linkedlifedata.com/resource/pubmed/chemical/Class Ib Phosphatidylinositol...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PIK3CG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Pik3cg protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor A,
http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor BB
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0950-9232
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pubmed:author |
pubmed-author:IlleiP BPB,
pubmed-author:LadanyiMM,
pubmed-author:MackallCC,
pubmed-author:MerchantM SMS,
pubmed-author:PassanitiAA,
pubmed-author:SunC JCJ,
pubmed-author:SunYY,
pubmed-author:ToretskyJ AJA,
pubmed-author:TsokosMM,
pubmed-author:UrenAA,
pubmed-author:VitoloM IMI
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pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2334-42
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12700668-Animals,
pubmed-meshheading:12700668-Bone Neoplasms,
pubmed-meshheading:12700668-Cell Division,
pubmed-meshheading:12700668-Chemotaxis,
pubmed-meshheading:12700668-Class Ib Phosphatidylinositol 3-Kinase,
pubmed-meshheading:12700668-Disease Progression,
pubmed-meshheading:12700668-Enzyme Inhibitors,
pubmed-meshheading:12700668-Humans,
pubmed-meshheading:12700668-Isoenzymes,
pubmed-meshheading:12700668-Mice,
pubmed-meshheading:12700668-Mice, SCID,
pubmed-meshheading:12700668-Neoplasm Proteins,
pubmed-meshheading:12700668-Neoplasm Transplantation,
pubmed-meshheading:12700668-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12700668-Phospholipase C gamma,
pubmed-meshheading:12700668-Phosphorylation,
pubmed-meshheading:12700668-Platelet-Derived Growth Factor,
pubmed-meshheading:12700668-Protein Processing, Post-Translational,
pubmed-meshheading:12700668-Receptor, Platelet-Derived Growth Factor beta,
pubmed-meshheading:12700668-Recombinant Proteins,
pubmed-meshheading:12700668-Sarcoma, Ewing,
pubmed-meshheading:12700668-Signal Transduction,
pubmed-meshheading:12700668-Tumor Cells, Cultured,
pubmed-meshheading:12700668-Type C Phospholipases,
pubmed-meshheading:12700668-Tyrphostins
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pubmed:year |
2003
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pubmed:articleTitle |
Beta-platelet-derived growth factor receptor mediates motility and growth of Ewing's sarcoma cells.
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pubmed:affiliation |
Lombardi Cancer Center, Georgetowm University Medical Center, Washington, DC 20057-1469, USA. au26@georgetown.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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