XXXX is a potent suppressor of osteosarcoma @entity3 .

@entity1 @entity66 @entity3478 @entity7 @entity51870 @entity421 @entity358 @entity3 @entity11436 @entity19877 @entity2044
@entity421 ( @entity421 ) accounts for 56% of @entity3478 in @entity1 and adolescents. @entity1 with @entity66 rarely develop @entity3 ; however, @entity358 occurs in approximately 50% of @entity1 and leads to a 5-year survival rate of only 10-20%. Therefore, identifying the genes and pathways involved in @entity3 , as new therapeutic targets, is crucial to improve long-term survival of @entity421 @entity1 . Novel markers that define metastatic @entity421 were identified using comparative transcriptomic analyses of two highly metastatic ( @entity51870 ) and two poorly metastatic clonal variants (C4 and C5) isolated from the metastatic @entity421 cell line, KHOS. Using this approach, we determined that the metastatic phenotype correlated with overexpression of @entity11436 ( @entity11436 ) or @entity7 ( @entity7 ). Validation in @entity1 biopsies confirmed @entity11436 and @entity7 targets were highly expressed in 29-42% of metastatic @entity421 @entity1 biopsies, with no detectable expression in non-malignant bone or samples from @entity421 @entity1 with @entity66 . @entity2044 (AF) was used to selectively target and inhibit @entity19877 ( @entity19877 ). At low doses, AF was able to inhibit @entity19877 activity without a significant effect on cell viability whereas at higher doses, AF could induce ROS-dependent apoptosis. AF treatment, in vivo, significantly reduced the development of @entity358 and we provide evidence that this effect may be due to an AF-dependent increase in cellular ROS. Thus, @entity11436 may represent a novel druggable target that could be deployed to reduce the development of fatal @entity358 in @entity1 with @entity421 .
