Development of Ewing's sarcoma from primary bone marrow-derived mesenchymal progenitor cells.

Details

Serval ID
serval:BIB_15B9430DD60D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Development of Ewing's sarcoma from primary bone marrow-derived mesenchymal progenitor cells.
Journal
Cancer research
Author(s)
Riggi N., Cironi L., Provero P., Suvà M.L., Kaloulis K., Garcia-Echeverria C., Hoffmann F., Trumpp A., Stamenkovic I.
ISSN
0008-5472
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
65
Number
24
Pages
11459-68
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
Ewing's sarcoma is a member of Ewing's family tumors (EFTs) and the second most common solid bone and soft tissue malignancy of children and young adults. It is associated in 85% of cases with the t(11;22)(q24:q12) chromosomal translocation that generates fusion of the 5' segment of the EWS gene with the 3' segment of the ETS family gene FLI-1. The EWS-FLI-1 fusion protein behaves as an aberrant transcriptional activator and is believed to contribute to EFT development. However, EWS-FLI-1 induces growth arrest and apoptosis in normal fibroblasts, and primary cells that are permissive for its putative oncogenic properties have not been discovered, hampering basic understanding of EFT biology. Here, we show that EWS-FLI-1 alone can transform primary bone marrow-derived mesenchymal progenitor cells and generate tumors that display hallmarks of Ewing's sarcoma, including a small round cell phenotype, expression of EFT-associated markers, insulin like growth factor-I dependence, and induction or repression of numerous EWS-FLI-1 target genes. These observations provide the first identification of candidate primary cells from which EFTs originate and suggest that EWS-FLI-1 expression may constitute the initiating event in EFT pathogenesis.
Keywords
Animals, Bone Marrow Cells, Cell Transformation, Neoplastic, Cyclin-Dependent Kinase Inhibitor p19, Fibroblasts, Gene Expression Profiling, Humans, Insulin-Like Growth Factor I, Mesenchymal Stem Cells, Mice, Mice, Inbred BALB C, Mice, SCID, Oligonucleotide Array Sequence Analysis, Oncogene Proteins, Fusion, Phenotype, Proto-Oncogene Protein c-fli-1, Sarcoma, Ewing's, Stem Cells, Tumor Markers, Biological, Tumor Suppressor Protein p53
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2008 18:34
Last modification date
20/08/2019 12:44
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