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Updated: Oct 31, 2025
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Molecular mechanisms underpinning sarcomas and implications for current and future therapy
Victoria Damerell1, Michael S Pepper2, Sharon Prince3
1Division of Cell Biology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, South Africa.
Abstract:
Sarcomas are complex mesenchymal neoplasms with a poor prognosis. Their clinical management is highly challenging due to their heterogeneity and insensitivity to current treatments. Although there have been advances in understanding specific genomic alterations and genetic mutations driving sarcomagenesis, the underlying molecular mechanisms, which are likely to be unique for each sarcoma subtype, are not fully understood. This is in part due to a lack of consensus on the cells of origin, but there is now mounting evidence that they originate from mesenchymal stromal/stem cells (MSCs). To identify novel treatment strategies for sarcomas, research in recent years has adopted a mechanism-based search for molecular markers for targeted therapy which has included recapitulating sarcomagenesis using in vitro and in vivo MSC models. This review provides a comprehensive up to date overview of the molecular mechanisms that underpin sarcomagenesis, the contribution of MSCs to modelling sarcomagenesis in vivo, as well as novel topics such as the role of epithelial-to-mesenchymal-transition (EMT)/mesenchymal-to-epithelial-transition (MET) plasticity, exosomes, and microRNAs in sarcomagenesis. It also reviews current therapeutic options including ongoing pre-clinical and clinical studies for targeted sarcoma therapy and discusses new therapeutic avenues such as targeting recently identified molecular pathways and key transcription factors.
Insights
Sarcomas, cancers originating from mesenchymal stromal/stem cells (MSCs), present treatment challenges. Understanding their molecular mechanisms, including EMT/MET plasticity, exosomes, and microRNAs, is key to developing novel targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Sarcomas are heterogeneous mesenchymal neoplasms with poor prognoses and challenging clinical management.
- Current understanding of sarcoma molecular mechanisms and cell of origin is limited, though mesenchymal stromal/stem cells (MSCs) are implicated.
- Existing treatments are often ineffective due to sarcoma heterogeneity and insensitivity.
Purpose of the Study:
- To provide a comprehensive overview of sarcomagenesis molecular mechanisms.
- To explore the role of mesenchymal stromal/stem cells (MSCs) in modeling sarcomagenesis.
- To review novel aspects like EMT/MET plasticity, exosomes, and microRNAs in sarcoma development and discuss targeted therapeutic strategies.
Main Methods:
- Review of current literature on sarcomagenesis.
- Analysis of mesenchymal stromal/stem cell (MSC) models for in vitro and in vivo sarcomagenesis studies.
- Examination of pre-clinical and clinical studies on targeted sarcoma therapies.
Main Results:
- Sarcomagenesis involves complex molecular mechanisms, potentially unique to each subtype, with increasing evidence pointing to mesenchymal stromal/stem cells (MSCs) as cells of origin.
- Epithelial-to-mesenchymal-transition (EMT)/mesenchymal-to-epithelial-transition (MET) plasticity, exosomes, and microRNAs play significant roles in sarcomagenesis.
- Novel molecular pathways and key transcription factors are being identified for targeted therapy.
Conclusions:
- Understanding the molecular underpinnings of sarcomagenesis, particularly the role of MSCs and associated factors like EMT/MET, exosomes, and microRNAs, is crucial for developing effective targeted therapies.
- Recapitulating sarcomagenesis using MSC models aids in identifying novel therapeutic targets.
- Future research should focus on these molecular pathways and transcription factors to advance targeted sarcoma treatment options.
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