Characterization of human mesenchymal stem cells from ewing sarcoma patients. Pathogenetic implications

Area of Science:

• Oncology
• Stem Cell Biology
• Molecular Biology

Background:

• Ewing sarcoma (EWS) is a bone and soft tissue tumor of mesenchymal origin.
• The precise early events in EWS development remain unclear.
• Mesenchymal stem cells (MSC) are hypothesized as the cell of origin for EWS.

Purpose of the Study:

• To investigate the characteristics of MSC from EWS patients (MSC-P).
• To compare MSC-P with MSC from healthy donors (MSC-HD) and EWS cell lines.
• To determine if MSC-P harbor genetic alterations or express features indicative of early sarcomagenesis.

Main Methods:

• Characterization of MSC-P, MSC-HD, and EWS cell lines.
• Evaluation of EWS-FLI1 gene fusion and EWSR1 gene rearrangements in MSC-P using q-RT-PCR.
• Multiparameter quantitative analysis of MSC immunophenotypic markers (CD105, CD90, CD34, CD45) and EWS-specific features (CD99 expression).

Main Results:

• MSC-P lack the common EWSR1-FLI1 gene fusion and EWSR1 rearrangements.
• MSC-P exhibit greater similarity to MSC-HD than to EWS cells.
• While EWS cells and MSC share some features like CD99 expression, MSC are not sensitive to CD99 inhibition, unlike EWS cells.

Conclusions:

• MSC from EWS patients exhibit characteristics similar to healthy MSC.
• MSC-P are phenotypically distinct from EWS cells.
• These findings raise questions about the direct involvement of MSC in Ewing sarcoma development.