Abstract
One of the still open questions in Ewing sarcoma, a rare bone tumor with weak therapeutic options, is to identify the tumor-driving cell (sub) population and to understand the specifics in the biological network of these cells. This basic scientific insight might foster the development of more specific therapeutic target patterns. The experimental approach is based on a side population (SP) of Ewing cells, based on the model cell line CADO-ES1. The SP is established by flow cytometry and defined by the idea that tumor stem-like cells can be identified by the time-course in clearing a given artificial dye. The SP was characterized by a higher colony forming activity, by a higher differentiation potential, by higher resistance to cytotoxic drugs, and by morphology. Several SP and non-SP cell fractions and bone marrow-derived mesenchymal stem cell reference were analyzed by short read sequencing of the full transcriptome. The double-differential analysis leads to an altered expression structure of SP cells centered around the AP-1 and APC/c complex. The SP cells share only a limited proportion of the full mesenchymal stem cell stemness set of genes. This is in line with the expectation that tumor stem-like cells share only a limited subset of stemness features which are relevant for tumor survival.
Highlights
Ewing sarcoma is the second most frequent malignant bone cancer after osteosarcoma and was first described by James Ewing in 1921 [1]
Ewing sarcoma is characterized as a small round blue-cell undifferentiated aggressive tumor of the bone and occasionally soft tissues with a marked propensity for dissemination [4,5]
On the molecular level, Ewing sarcoma is characterized by aberrant chromosomal translocations usually involving EWSR1 (22q12), a gene belonging to the TET protein family, and one of the genes from ETS family of transcription factors
Summary
Ewing sarcoma is the second most frequent malignant bone cancer after osteosarcoma and was first described by James Ewing in 1921 [1]. The chimeric fusion proteins are produced when the N-terminal transactivation domain of EWSR1 combines with the C-terminal DNA binding domain of FLI-1 or ERG [7]. Both FLI1 and ERG share 68% amino acid identity over their entire peptide sequence and 98% (83/85) amino acid identity in their ETS-binding domains [10]. The other less frequent ETS-family translocation partners include ETV1 (7p22), ETV4/E1AF (17q12) and FEV (2q33) genes [11]. These mentioned main features of the Ewing sarcoma form the mature appearance of the tumor when diagnosed in the clinic
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