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Updated: Jan 13, 2026
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Proteomics analysis of human mesenchymal stromal/stem cell sarcomagenesis model identifies ALDH1A3 and CD99 as
Jonathan M Gobin1,2, Jun Gao2, Veronica Rey3,4,5
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Background:
Mesenchymal stromal/stem cells (MSC) may represent the cell-of-origin for sarcoma development. A collection of human MSCs sequentially mutated with an increasing number of oncogenic hits served to recreate a step-wise process of sarcomagenesis. To identify potential protein targets of interest in the MSC-sarcoma transformation process, quantitative mass spectrometry-based (LC-MS/MS) proteomics was performed.
Results:
Among the protein hits identified as significantly regulated in the transformation process, ALDH1A3 and CD99 were selected and further studied. Both ALDH1A3 abundance levels and activity were significantly upregulated in early-phase (immortalized) and fully transformed (sarcoma forming) cells as compared to normal MSCs. Inversely, CD99 total protein and cell-surface abundance levels were downregulated in immortalized and transformed MSCs. Downregulated CD99 was also identified in several human bone and soft tissue sarcoma subtypes.
Conclusions:
Proteomics investigation of a MSC-transformation model of sarcoma has yielded ALDH1A3 and CD99 as potential targets for sarcomagenesis that may contribute to a greater understanding of the disease and the development of novel therapeutic approaches.
Insights
Researchers identified Aldehyde Dehydrogenase 1 Family Member A3 (ALDH1A3) and CD99 as key proteins in sarcoma development from mesenchymal stem cells (MSCs). Upregulated ALDH1A3 and downregulated CD99 indicate their roles in cancer progression and potential therapeutic targets.
Area of Science:
- Oncology
- Stem Cell Biology
- Proteomics
Background:
- Mesenchymal stromal/stem cells (MSCs) are implicated as the cell-of-origin for sarcoma.
- A stepwise model of sarcomagenesis was created using sequentially oncogenically mutated human MSCs.
Purpose of the Study:
- To identify protein targets involved in the transformation of MSCs into sarcoma.
- To investigate the roles of ALDH1A3 and CD99 in sarcomagenesis.
Main Methods:
- Quantitative mass spectrometry-based (LC-MS/MS) proteomics was employed.
- ALDH1A3 and CD99 expression and activity were analyzed in normal MSCs, immortalized cells, and sarcoma cells.
Main Results:
- ALDH1A3 abundance and activity were significantly upregulated in early-phase and transformed cells compared to normal MSCs.
- CD99 protein and cell-surface levels were downregulated in immortalized and transformed MSCs.
- Downregulated CD99 was observed in human bone and soft tissue sarcoma subtypes.
Conclusions:
- Proteomics analysis of an MSC-sarcoma transformation model identified ALDH1A3 and CD99 as potential sarcomagenesis targets.
- These proteins may enhance understanding of sarcoma development.
- ALDH1A3 and CD99 represent potential targets for novel therapeutic strategies in sarcoma.
