|
| Status |
Public on Jun 18, 2013 |
| Title |
Expression of FUS-CHOP fusion protein in immortalized/transformed human Mesenchymal Stem Cells drives mixoid liposarcoma formation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Although different sarcomas have been modeled in mice upon expression of fusion oncogenes in MSCs, sarcomagenesis has not been successfully modeled in human MSCs (hMSCs). We report that FUS-CHOP, a hallmark fusion gene in mixoid liposarcoma (MLS), has an instructive role in lineage commitment, and its expression in hMSC sequentially immortalized/transformed with up to 5 oncogenic hits (p53 and Rb deficiency, hTERT over-expression, c-myc stabilization and H-RASv12 mutation) drives the formation of serially transplantable MLS. This is the first model of sarcoma based on the expression of a sarcoma-associated fusion protein in hMSC, and allowed us to unravel the differentiation processes and signaling pathways altered in the MLS-initiating cells. This study will contribute to test novel therapeutic approaches, and constitutes a proof-of-concept to employ hMSCs as target cell for modeling other fusion gene-associated human sarcomas.
|
| |
|
| Overall design |
Wild type (MSC-0H) or transformed (MSC-5H) BM-hMSCs were transduced with concentrated viral particles expressing either pRRL-EF1α-PGK-GFP (empty vector; GFP) or pRRL-EF1α-FUS-CHOP-PGK-GFP (FUSCHOP expressing vector; FC) in order to generate MSC-0H-GFP, MSC-0H-FC, MSC-5H-GFP and MSC-5H-FC cell lines. MSC-0H-GFP and MSC-0H-FC cells did not develop tumors, meanwhile MSC-5H-GFP cells gave rise to undifferentiated sarcomas and MSC-5H-FC originated mixoid liposarcoma tumors when inoculated into immunedeficient mice. Several cell lines were derived from tumors developed from MSC-5H-GFP (T-5H-GFP-1 to -3 cell lines) and MSC-5H-FC (T-5H-FC-1 to -3 cell lines) cells. Gene expression analysis was performed using MSC-0H, MSC-5H and T-5H cell lines and lists of differentially expressed genes were created by comparing the gene expression profiles of MSC-0H-FC, MSC-5H-FC and T-5H-FC cell types to the control MSC-0H-GFP cells.
|
| |
|
| Contributor(s) |
Rodriguez R, Menendez P |
| Citation(s) |
23836491 |
| Submission date |
Jun 17, 2013 |
| Last update date |
Oct 11, 2016 |
| Contact name |
Rene Rodriguez |
| Organization name |
Hospital Universitario Central de Asturias & Instituto Universitario de Oncologia de Asturias (IUOPA)
|
| Street address |
C/ Celestino Villamil s/n
|
| City |
Oviedo |
| ZIP/Postal code |
33006 |
| Country |
Spain |
| |
|
| Platforms (1) |
| GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
|
| Samples (16)
|
|
| Relations |
| BioProject |
PRJNA208727 |
Less...
More...