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

Laboratory of Experimental Oncology, CRS Development of Biomolecular Therapies, SSN Emilia Romagna Istituti Ortopedici Rizzoli IRCCS, Bologna, Italy.
The Journal of clinical investigation (Impact Factor: 13.77). 02/2010; 120(3):668-80. DOI: 10.1172/JCI36667
Source: PubMed

ABSTRACT 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 form tumors and bone metastases when xenografted into immunodeficient mice and diminished their tumorigenic characteristics in vitro. Further, reduction of CD99 expression resulted in neurite outgrowth and increased expression of beta-III tubulin and markers of neural differentiation. Analysis of a panel of human EWS cells revealed an inverse correlation between CD99 and H-neurofilament expression, as well as an inverse correlation between neural differentiation and oncogenic transformation. As knockdown of CD99 also led to an increase in phosphorylation of ERK1/2, we suggest that the CD99-mediated prevention of neural differentiation of EWS occurs through MAPK pathway modulation. Together, these data indicate a new role for CD99 in preventing neural differentiation of EWS cells and suggest that blockade of CD99 or its downstream molecular pathway may be a new therapeutic approach for EWS.

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Available from: Mario P Colombo, Jan 18, 2014
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    • "Recent data suggest that CD99 is not only a marker and therapeutic target for Ewing's sarcoma, but may also contribute to the disease phenotype. Knockdown of CD99 in Ewing's sarcoma cell lines resulted in decreased growth in tissue culture, diminished colony formation in soft agar assays, reduced cell motility, and smaller tumors with less metastasis in xenograft models (Rocchi et al., 2010). This study also suggested that CD99 inhibits full neuronal differentiation by decreasing the activity of the MAP kinase pathway. "
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