Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium

MacFadyen, John R.; Haworth, Oliver; Roberston, David; Hardie, Deborah; Webster, Marie-Thérèse; Morris, Howard R.; Panico, Maria; Sutton-Smith, Mark; Dell, Anne; Geer, Peter van der; Wienke, Dirk; Buckley, Christopher D.; Isacke, Clare M.

doi:10.1016/j.febslet.2005.03.071

Cited by 154 publications

(174 citation statements)

References 25 publications

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“…7 In cultured cells, expression of endosialin has only been reported on fibroblasts and some neuroblastoma cell lines. [6][7][8][9] This pattern is reflected in normal adult tissue, where endosialin expression is predominantly restricted to stromal fibroblasts, and in agreement with the SAGE analysis of St Croix et al 5 little or no endosialin is detected in the mature, normal vasculature. [9][10][11][12][13] In contrast, there is a marked upregulation of endosialin expression in the angiogenic vasculature of a wide variety of different tumor types including those of the brain, colon, breast and in tumor xenografts.…”

supporting

confidence: 86%

“…[6][7][8][9] This pattern is reflected in normal adult tissue, where endosialin expression is predominantly restricted to stromal fibroblasts, and in agreement with the SAGE analysis of St Croix et al 5 little or no endosialin is detected in the mature, normal vasculature. [9][10][11][12][13] In contrast, there is a marked upregulation of endosialin expression in the angiogenic vasculature of a wide variety of different tumor types including those of the brain, colon, breast and in tumor xenografts. 6,9,11,12,14,15 However, there is controversy between these reports as to whether this upregulation is due to expression by the endothelial cells and/or the perivascular cells.…”

supporting

confidence: 86%

“…[9][10][11][12][13] In contrast, there is a marked upregulation of endosialin expression in the angiogenic vasculature of a wide variety of different tumor types including those of the brain, colon, breast and in tumor xenografts. 6,9,11,12,14,15 However, there is controversy between these reports as to whether this upregulation is due to expression by the endothelial cells and/or the perivascular cells. Two major difficulties have arisen in resolving this controversy.…”

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confidence: 99%

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Endosialin (CD248) is a marker of tumor-associated pericytes in high-grade glioma

et al. 2008

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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.

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supporting

confidence: 86%

supporting

confidence: 86%

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confidence: 99%

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Endosialin (CD248) is a marker of tumor-associated pericytes in high-grade glioma

et al. 2008

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“…Later, endosialin was found to be expressed in the vasculature and fibroblasts of human brain tumor specimens, including astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, meningioma, oligodendroglioma, ependymoma and carcinoma brain metastasis 6263. By immunohistochemistry, endosialin co-localized with the pericyte marker NG2 in breast cancer specimens but not with the endothelial marker CD31 5657. In carcinomas, endosialin protein was detected in tumor capillaries and fibroblasts 53.…”

Section: Sarcoma Targetsmentioning

confidence: 99%

“…High endosialin was detected in fibroblasts and pericytes in human thymus, lymph nodes and spleen during lymphoid tissue development but mostly absent in the adult except during secondary lymphoid organ remodeling during adaptive immune responses 5455. In normal adults, endosialin protein expression appears to be limited to normal endometrial stroma and occasional fibroblasts 535657. The murine ortholog of endosialin was cloned and found to be expressed during development and during implanted tumor growth in the adult mouse 5859…”

Section: Sarcoma Targetsmentioning

confidence: 99%

Characteristics of human Ewing/PNET sarcoma models

Teicher¹,

Rouleau²,

Kruger³

et al. 2011

Annals of Saudi Medicine

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Ewing/PNET (peripheral neuroepithelioma) tumors are rare aggressive bone sarcomas occurring in young people. Rare-disease clinical trials can require global collaborations and many years. In vivo models that as accurately as possible reflect the clinical disease are helpful in selecting therapeutics with the most promise of positive clinical impact. Human Ewing/PNET sarcoma cell lines developed over the past 45 years are described. Several of these have undergone genetic analysis and have been confirmed to be those of Ewing/PNET sarcoma. The A673 Ewing sarcoma line has proven to be particularly useful in understanding the biology of this disease in the mouse. The chromosomal translocation producing the EWS/FLI1 fusion transcript characterizes clinical Ewing sarcoma. Cell lines that express this genetic profile are confirmed to be those of Ewing sarcoma. The A673 Ewing sarcoma line grows in culture and as a xenograft in immunodeficient mice. The A673 model has been used to study Ewing sarcoma angiogenesis and response to antiangiogenic agents. Many Ewing sarcoma clinical specimens express the cell surface protein endosialin. Several Ewing sarcoma cell lines, including the A673 line, also express cell surface endosialin when grown as subcutaneous tumor nodules and as disseminated disease; thus the A673 is a useful model for the study of endosialin biology and endosialin-directed therapies. With the advent of tools that allow characterization of clinical disease to facilitate optimal treatment, it becomes imperative, especially for rare tumors, to develop preclinical models reflecting disease subsets. Ewing PNET sarcomas are a rare disease where models are available.

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CD248 and its cytoplasmic domain: A therapeutic target for arthritis

Maia¹,

Vriese²,

Janssens³

et al. 2010

Arthritis & Rheumatism

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Objective. CD248 is a transmembrane glycoprotein expressed on the surface of activated perivascular and fibroblast-like cells. This study was undertaken to explore the function of CD248 and its cytoplasmic domain in arthritis.Methods. Synovial tissue biopsy samples from healthy controls, from patients with psoriatic arthritis (PsA), and from patients with rheumatoid arthritis (RA) were stained for CD248. Transgenic mice that were CD248-deficient (CD248-knockout [CD248 KO/KO ]) or mice with CD248 lacking the cytoplasmic domain (CD248 CyD/CyD ) were generated. Collagen antibodyinduced arthritis (CAIA) was induced in these mice and in corresponding wild-type (WT) mice as controls. Clinical signs and histologic features of arthritis were evaluated. Cytokine levels were determined by enzymelinked immunosorbent assay, and the number of infiltrating inflammatory cells was quantified by immunohistochemistry. In vitro studies were performed with fibroblasts from CD248-transgenic mouse embryos to explain the observed effects on inflammation.Results. Immunostaining of synovium from patients with PsA and patients with RA and that from mice after the induction of CAIA revealed strong CD248 expression in perivascular and fibroblast-like stromal cells. CD248 KO/KO and CD248 CyD/CyD mice had less severe arthritis, with lower plasma levels of proinflammatory cytokines, as compared with WT controls. Moreover, the joints of these mice had less synovial hyperplasia, reduced accumulation of inflammatory cells, and less articular cartilage and bone damage. Tumor necrosis factor ␣-induced monocyte adhesion to CD248 CyD/CyD fibroblasts was impaired. CD248 CyD/CyD fibroblasts exhibited reduced expression of hypoxia-inducible factor 1␣, placental growth factor, vascular endothelial growth factor, and matrix metalloproteinase 9 activity in response to transforming growth factor ␤.Conclusion. CD248 contributes to synovial hyperplasia and leukocyte accumulation in inflammatory arthritis, the effects of which are mediated partly via its cytoplasmic domain. CD248 is therefore a potential new target in the treatment of arthritis.

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Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium

Cited by 154 publications

References 25 publications

Endosialin (CD248) is a marker of tumor-associated pericytes in high-grade glioma

Endosialin (CD248) is a marker of tumor-associated pericytes in high-grade glioma

Characteristics of human Ewing/PNET sarcoma models

CD248 and its cytoplasmic domain: A therapeutic target for arthritis

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