title: Endosialin (CD248) is a marker of tumor-associated pericytes in high-grade glioma.
abstract: Gliomas are the most frequent primary tumors of the central nervous system in adults. The most prevalent and aggressive subclass of these is glioblastoma multiforme, which is characterized by massive neovascularization. Endosialin (CD248) has generated interest as a target for antiangiogenic therapy following reports that its expression is upregulated on angiogenic endothelial cells. We demonstrate here that endosialin is not expressed in normal human adult brain but is strongly upregulated in the angiogenic vasculature of all high-grade glioma specimens examined. However, by taking advantage of a technique which allows for multiple fluorescent labeling of formalin-fixed paraffin-embedded archival sections, we demonstrate unambiguously that endosialin is not expressed by the glioma endothelial cells but on closely associated perivascular cells. With increasing awareness that targeting pericytes is an attractive adjunct in antiangiogenic therapy, this finding has important implications for understanding the molecular mechanisms regulating angiogenesis in these highly vascularized tumors.
authors.affiliation: 1Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Simonavicius
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.forename: Dorine A
authors.initials: DA
authors.lastname: Bax
authors.forename: Chris
authors.initials: C
authors.lastname: Jones
authors.forename: Ivo J
authors.initials: IJ
authors.lastname: Huijbers
authors.forename: Clare M
authors.initials: CM
authors.lastname: Isacke
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D001932:Brain Neoplasms / Q000098:blood supply* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005909:Glioblastoma / Q000098:blood supply* / Q000473:pathology; D005910:Glioma / Q000098:blood supply* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D020286:Pericytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; C078203:CD248 protein, human