CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis

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CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis.

Ewing sarcoma (EWS) is an aggressive bone tumor of uncertain cellular origin. CD99 is a membrane protein that is expressed in most cases of EWS, although its function in the disease is unknown. Here we have shown that endogenous CD99 expression modulates EWS tumor differentiation and malignancy. We determined that knocking down CD99 expression in human EWS cell lines reduced their ability to fo...

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Modeling Initiation of Ewing Sarcoma in Human Neural Crest Cells

Ewing sarcoma family tumors (ESFT) are aggressive bone and soft tissue tumors that express EWS-ETS fusion genes as driver mutations. Although the histogenesis of ESFT is controversial, mesenchymal (MSC) and/or neural crest (NCSC) stem cells have been implicated as cells of origin. For the current study we evaluated the consequences of EWS-FLI1 expression in human embryonic stem cell-derived NCS...

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CD99 triggering induces methuosis of Ewing sarcoma cells through IGF-1R/RAS/Rac1 signaling

CD99 is a cell surface molecule that has emerged as a novel target for Ewing sarcoma (EWS), an aggressive pediatric bone cancer. This report provides the first evidence of methuosis in EWS, a non-apoptotic form of cell death induced by an antibody directed against the CD99 molecule. Upon mAb triggering, CD99 induces an IGF-1R/RAS/Rac1 complex, which is internalized into RAB5-positive endocytic ...

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Targeted Imaging of Ewing Sarcoma in Preclinical Models Using a Cu-Labeled Anti-CD99 Antibody

Purpose: Ewing sarcoma is a tumor of the bone and soft tissue characterized by diffuse cell membrane expression of CD99 (MIC2). Single-site, surgically resectable disease is associated with an excellent 5-year event-free survival; conversely, patientswith distantmetastases have a poor prognosis.Noninvasive imaging is the standard approach to identifying sites of metastatic disease. We sought to...

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Ewing sarcoma with extensive neural differentiation: a clinicopathologic, immunohistochemical, and molecular analysis of three cases.

OBJECTIVES Three patients with Ewing sarcomas showing extensive neural differentiation are presented. METHODS The patients were two women and one man between the ages of 15 and 35 years. Anatomically, one tumor was in the lung, one in the testis, and one in the cervix uteri. The symptoms were determined by the location of the neoplasm and included respiratory symptoms, testicular pain, and pe...

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 2010

ISSN: 0021-9738

DOI: 10.1172/jci36667