http://purl.uniprot.org/citations/19948061 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/19948061 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundTEM1/endosialin is an emerging microvascular marker of tumor angiogenesis. We characterized the expression pattern of TEM1/endosialin in astrocytic and metastatic brain tumors and investigated its role as a therapeutic target in human endothelial cells and mouse xenograft models.MethodsIn situ hybridization (ISH), immunohistochemistry (IH) and immunofluorescence (IF) were used to localize TEM1/endosialin expression in grade II-IV astrocytomas and metastatic brain tumors on tissue microarrays. Changes in TEM1/endosialin expression in response to pro-angiogenic conditions were assessed in human endothelial cells grown in vitro. Intracranial U87MG glioblastoma (GBM) xenografts were analyzed in nude TEM1/endosialin knockout (KO) and wildtype (WT) mice.ResultsTEM1/endosialin was upregulated in primary and metastatic human brain tumors, where it localized primarily to the tumor vasculature and a subset of tumor stromal cells. Analysis of 275 arrayed grade II-IV astrocytomas demonstrated TEM1/endosialin expression in 79% of tumors. Robust TEM1/endosialin expression occurred in 31% of glioblastomas (grade IV astroctyomas). TEM1/endosialin expression was inversely correlated with patient age. TEM1/endosialin showed limited co-localization with CD31, alphaSMA and fibronectin in clinical specimens. In vitro, TEM1/endosialin was upregulated in human endothelial cells cultured in matrigel. Vascular Tem1/endosialin was induced in intracranial U87MG GBM xenografts grown in mice. Tem1/endosialin KO vs WT mice demonstrated equivalent survival and tumor growth when implanted with intracranial GBM xenografts, although Tem1/endosialin KO tumors were significantly more vascular than the WT counterparts.ConclusionTEM1/endosialin was induced in the vasculature of high-grade brain tumors where its expression was inversely correlated with patient age. Although lack of TEM1/endosialin did not suppress growth of intracranial GBM xenografts, it did increase tumor vascularity. The cellular localization of TEM1/endosialin and its expression profile in primary and metastatic brain tumors support efforts to therapeutically target this protein, potentially via antibody mediated drug delivery strategies."xsd:string |
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http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/author | "Tyler B.M."xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/author | "Walter K.A."xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/author | "Carson-Walter E.B."xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/author | "Johnson M.D."xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/author | "Huso D.L."xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/author | "Whiteman M.C."xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/author | "Haapasalo H."xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/author | "Jarvela S."xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/author | "Winans B.N."xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/name | "BMC Cancer"xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/pages | "417"xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/title | "Characterization of TEM1/endosialin in human and murine brain tumors."xsd:string |
http://purl.uniprot.org/citations/19948061 | http://purl.uniprot.org/core/volume | "9"xsd:string |
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