Xg Expression in Ewing's Sarcoma Is of Prognostic Value and Contributes to Tumor Invasiveness

Abstract

Ewing's sarcoma (EWS) is an aggressive tumor of children and young adults that requires intensive treatment. The search for new prognostic factors is very important to choose the most appropriate therapy and to better understand the biology of the disease for the development of new therapeutic tools. We found that Xg, a thus far poorly described molecule and member of the CD99 family, is expressed in EWS cell lines and EWS primary tumors. Immunohistochemical analysis confirmed the expression of Xg in 24% of patients. We found that Xg expression in EWS defines a subgroup of patients with worse prognosis compared with those with Xgnegative localized tumors, indicating a clinical relevance of Xg expression in EWS. Forced expression of Xg in an EWS cell line upregulated cell migration and invasion in vitro. Furthermore, knockdown of Xg expression with specific short hairpin RNA significantly reduced migration and invasion of EWS cells. Consistent with these data, in vivo xenotransplant studies in nude mice revealed that Xg expression increased the incidence and the number of metastases of EWS cells. Thus, Xg expression is associated with lower overall survival in EWS patients with localized tumors and is implicated in metastasis. Cancer Res; 70(9); 3730-8. ©2010 AACR.

Targeting the EWSR1-FLI1 Oncogene-Induced Protein Kinase PKC-β Abolishes Ewing Sarcoma Growth

“…1A). Among the top 100 probe sets found to be specific for Ewing sarcoma (see Supplementary Table S1), several represented genes that were previously identified as important for Ewing tumors such as NKX2-2 (10), NR0B1 (8,9), LIPI (28), DKK2 (29), or XG (30), and most of them were previously identified as EWSR1-FLI1-dependent genes (4,15,31). Among these genes, we focused our attention on the PRKCB for which 5 probe sets (Fig.…”

A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xgnull phenotype, underlying anti‐Xga production

“…XG is homologous to CD99 and therefore it is speculated they share similar cell adhesion and migration functions . Indeed, in Ewing's sarcoma, XG expression is associated with cell migration, invasion, and a poorer prognosis . However, little is known about the function of XG in healthy people.…”

Xg Blood Group System

“…CD99 is expressed at the cell surface in most cases of Ewing sarcoma (EWS), a malignant, aggressive bone tumour, and is the best diagnostic marker for this disease [93] . Knocking down of CD99 expression in human EWS cell lines reduced their ability to form tumours and bone metastases when grafted into immunodefi cient mice [94] ; Xg a expression increased the number of metastases [95] . Whereas 100% of EWS tumours express CD99, tumours in 24% of EWS patients also express Xg a , which defi nes a subgroup of patients with worse prognosis than those not expressing Xg a [95] .…”

“…CD99 is expressed at around 8 -fold higher levels on acute lymphoblastic leukaemia lymphoblasts than on normal T cells and could be used as a marker for minimal residual disease [92] . Whereas 100% of EWS tumours express CD99, tumours in 24% of EWS patients also express Xg a , which defi nes a subgroup of patients with worse prognosis than those not expressing Xg a [95] . CD99 contributes to oncogenesis by preventing neural differentiation through modulation of a mitogenactive protein kinase pathway [94] .…”