title: Endosialin (Tem1) is a marker of tumor-associated myofibroblasts and tumor vessel-associated mural cells.
abstract: Endosialin (Tem1) has been identified by two independent experimental approaches as an antigen of tumor-associated endothelial cells, and it has been claimed to be the most abundantly expressed tumor endothelial antigen, making it a prime candidate for vascular targeting purposes. Recent experiments have challenged the endothelial expression of endosialin and suggested an expression by activated fibroblasts and pericytes. Thus, clarification of the controversial cellular expression of endosialin is critically important for an understanding of its role during tumor progression and its validation as a potential therapeutic target. We have therefore performed extensive expression profiling analyses of endosialin. The experiments unambiguously demonstrate that endosialin is expressed by tumor-associated myofibroblasts and mural cells and not by endothelial cells. Endosialin expression is barely detectable in normal human tissues with moderate expression only detectable in the stroma of the colon and the prostate. Corresponding cellular experiments confirmed endosialin expression by mesenchymal cells and indicated that it may in fact be a marker of mesenchymal stem cells. Silencing endosialin expression in fibroblasts strongly inhibited migration and proliferation. Collectively, the experiments validate endosialin as a marker of tumor-associated myofibroblasts and tumor vessel-associated mural cells. The data warrant further functional analysis of endosialin during tumor progression and its exploitation as marker of tumor vessel-associated mural cells, expression of which may reflect the non-normalized phenotype of the tumor vasculature.
authors.affiliation: Department of Vascular Oncology and Metastatis, University of Heidelberg, Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Christian
authors.forename: Renate
authors.initials: R
authors.lastname: Winkler
authors.forename: Iris
authors.initials: I
authors.lastname: Helfrich
authors.forename: Anja M
authors.initials: AM
authors.lastname: Boos
authors.forename: Eva
authors.initials: E
authors.lastname: Besemfelder
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.forename: Hellmut G
authors.initials: HG
authors.lastname: Augustin
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001808:Blood Vessels / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C078203:CD248 protein, human; D012333:RNA, Messenger