Epigenetic reprogramming and re-differentiation of a Ewing sarcoma cell line.

摘要: Developmental reprogramming techniques have been used to generate induced pluripotent stem (iPS) cells from both normal and malignant cells. The derivation of iPS cancer has the potential provide a unique scientific tool overcome challenges associated with establishment cell lines primary patient samples readily expandable source that may be model initial disease. In current study we developmentally reprogrammed metastatic Ewing sarcoma (EWS) line meta-stable embryonic (ES)-like state sharing molecular phenotypic features previously established ES lines. EWS-iPS exhibited pronounced drug resistant phenotype despite persistent expression oncogenic EWS-FLI1 fusion transcript. This included resistance compounds specifically target downstream effector pathways EWS-FLI1, such as MAPK/ERK PI3K/AKT, which play an important role in EWS pathogenesis. displayed tumor initiation abilities vivo formed tumors exhibiting characteristic histopathology. parallel, re-differentiated vitro recovered sensitivity molecularly targeted chemotherapeutic agents, reiterated pathophysiological they were derived. These data suggest disease could investigate processes modulating oncogenesis, metastasis, EWS.