Defining a Characteristic Gene Expression Set Responsible for Cancer Stem Cell-Like Features in a Sub-Population of Ewing Sarcoma Cells CADO-ES1

• Published in: International journal of molecular sciences Vol. 19; no. 12; p. 3908
• Main Authors: Hotfilder, Marc, Mallela, Nikhil, Seggewiß, Jochen, Dirksen, Uta, Korsching, Eberhard
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.12.2018; MDPI
• Subjects: Adenomatous polyposis coli; AP-1; APC/c; Bone marrow; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone tumors; Cancer; cancer stem cells; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cytology; Cytotoxicity; Drug development; Drug resistance; Drug Resistance, Neoplasm; Epigenesis, Genetic; Ewing sarcoma; Ewing's sarcoma; Ewings sarcoma; Flow Cytometry; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Medical prognosis; mesenchymal stem cells; Mesenchyme; Neoplastic Stem Cells - metabolism; Population; Sarcoma, Ewing - genetics; Sarcoma, Ewing - metabolism; Sequence Analysis, RNA; side population; Side-Population Cells - metabolism; Stem cells; Transcription factors; Transcriptomes; tumor driver cells; Tumors; side population; APC/c; Ewing sarcoma; mesenchymal stem cells; cancer stem cells; tumor driver cells; AP-1; gene expression
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19123908

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.