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Cecile Rouleau,
Robert Smale,
Yao-Shi Fu,
Guodong Hui,
Fei Wang,
Elizabeth Hutto,
Robert Fogle,
Craig M Jones,
Roy Krumbholz,
Stephanie Roth,
Maritza Curiel,
Yi Ren,
Rebecca G Bagley, Gina Wallar,
Glenn Miller,
Steven Schmid,
Bruce Horten,
Beverly A Teicher
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ABSTRACT: We previously surveyed the expression of endosialin/ CD248/TEM-1 by immunohistochemistry in human clinical specimens of sarcomas and documented expression in tumor cells, stromal cells and vasculature. In the present study, we completed a retrospective analysis of the diagnostic reports available for these same samples in order to identify high-grade and metastatic disease. Our results show that endosialin can be detected in advanced disease. We screened human sarcoma cell lines in vitro for endosialin expression and developed preclinical human xenograft models of disseminated sarcoma. We found that 22 out of 42 human sarcoma cell lines were positive for endosialin with a positive correlation between mRNA and protein levels. When implanted in vivo, endosialin was expressed at all sites of dissemination. These data provide clinical and preclinical evidence that endosialin can be detected in advanced sarcoma. These results demonstrate for the first time that endosialin is a suitable therapeutic target for poor prognosis and advanced disease.
International Journal of Oncology 07/2011; 39(1):73-89. · 2.40 Impact Factor
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Cecile Rouleau,
Robert Smale,
Jose Sancho,
Yao-Shi Fu,
Leslie Kurtzberg,
William Weber,
Ariel Kruger,
Craig Jones,
Stephanie Roth,
Christy Bormann,
Sarah Dunham,
Roy Krumbholz,
Maritza Curiel, Gina Wallar,
James Mascarello,
Juanita Campos-Rivera,
Bruce Horten,
Steven Schmid,
Glenn Miller,
Beverly A Teicher
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ABSTRACT: Endosialin emerged recently as a potential therapeutic target for sarcoma. Since some sarcoma subtypes, such as Ewing's sarcoma, show characteristics of neuroendocrine differentiation, we wondered whether cancers with neuro-endocrine properties and/or neuroectodermal origin, such as neuroblastoma, small cell lung cancer and melanoma, may express endosialin. Endosialin protein expression was surveyed in neuroblastoma, small cell lung cancer and melanoma in human clinical specimens by immunohistochemistry (IHC) and in human cell lines by flow cytometry. Side population cells were examined to determine whether cancer stem cells can express endosialin. Endosialin-expressing neuroblastoma cell lines were implanted in immunodeficient mice and allowed to grow. The xenograft tumors were resected and tested for endosialin expression by IHC. In human clinical specimens, vascular endosialin staining was observed in neuroblastoma, small cell lung cancer and melanoma. Malignant cell staining was strongest in neuroblastoma, weak in melanoma and rare in small cell lung cancer. In human cell lines, endosialin was detected in neuroblastoma cell lines, including cancer stem cell-like side population (SP) cells, but was absent in melanoma and was both rare and weak in small cell lung cancer. Human neuroblastoma xenograft tumors were found to be positive for endosialin. Our work suggests that endosialin may be a suitable therapeutic target for neuroblastoma.
International Journal of Oncology 06/2011; 39(4):841-51. · 2.40 Impact Factor
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Cecile Rouleau,
Maritza Curiel,
William Weber,
Robert Smale,
Leslie Kurtzberg,
James Mascarello,
Carol Berger, Gina Wallar,
Rebecca Bagley,
Nakayuki Honma,
Kazumasa Hasegawa,
Isao Ishida,
Shiro Kataoka,
Beth L Thurberg,
Khodadad Mehraein,
Bruce Horten,
Glenn Miller,
Beverly A Teicher
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ABSTRACT: Endosialin/CD248/tumor endothelial marker 1 is expressed in stromal cells, endothelial cells, and pericytes in various tumors; however, few studies have focused on expression in malignant cells.
We studied expression of endosialin in clinical specimens, cell culture, and animal models and designed an anti-endosialin therapeutic prototype.
Fifty human tumor cell lines and 6 normal cell types in culture were assayed by reverse transcription-PCR and/or flow cytometry for endosialin. Cell surface protein was found on 7 sarcoma lines, 1 neuroblastoma, and 4 normal cell types in culture. A fully human anti-endosialin antibody bound to human A-673 Ewing's sarcoma cells and SK-N-AS neuroblastoma cells but not HT-1080 cells. Exposure of cells to an anti-human IgG conjugated to saporin resulted in growth inhibition only of endosialin-expressing cells. Endosialin expression was assessed by immunohistochemistry in 250 clinical specimens of human cancer including 20 cancer subtypes. Endosialin is frequently found in human cancers. Endosialin expression is mainly a perivascular feature in carcinomas, with some expression in stromal cells. In sarcomas, endosialin is expressed by malignant cells, perivascular cells, and stromal cells. Development and characterization of experimental models for studying endosialin biology in sarcomas and evaluating anti-endosialin therapies is presented.
Findings suggest that an anti-endosialin immunotoxin might be a promising therapeutic approach for endosialin-positive neoplasia, especially synovial sarcoma, fibrosarcoma, malignant fibrous histiocytoma, liposarcoma, and osteosarcoma. Thus, a diagnostic/therapeutic targeted therapeutic approach to treatment of endosialin-expressing tumors may be possible.
Clinical Cancer Research 12/2008; 14(22):7223-36. · 7.74 Impact Factor
