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http://purl.uniprot.org/citations/19948061http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19948061http://www.w3.org/2000/01/rdf-schema#comment"

Background

TEM1/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.

Methods

In 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.

Results

TEM1/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.

Conclusion

TEM1/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/19948061http://purl.uniprot.org/core/author"Liu Y."xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/author"Tyler B.M."xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/author"Walter K.A."xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/author"Carson-Walter E.B."xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/author"Johnson M.D."xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/author"Huso D.L."xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/author"Whiteman M.C."xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/author"Haapasalo H."xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/author"Jarvela S."xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/author"Winans B.N."xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/name"BMC Cancer"xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/pages"417"xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/title"Characterization of TEM1/endosialin in human and murine brain tumors."xsd:string
http://purl.uniprot.org/citations/19948061http://purl.uniprot.org/core/volume"9"xsd:string
http://purl.uniprot.org/citations/19948061http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19948061
http://purl.uniprot.org/citations/19948061http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19948061
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