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Updated: Jun 5, 2025
Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts
Published on: June 13, 2019
Targeted transcriptomic analysis of well-differentiated and dedifferentiated liposarcoma reveals multiple
Ashley Patton1, Natalie Horn1, Puja Upadhaya1
1Department of Pathology and Laboratory Medicine, The Ohio State University Medical Center, Columbus, OH, United States.
Abstract:
Liposarcoma is the most prevalent sarcoma in adults representing 20% of all sarcomas with well-differentiated/dedifferentiated among the most common subtypes represented. Despite multimodality treatment approaches, there has not been any appreciable change in survival benefit in the past 10 years. The future of targeted therapy for WD/DDLPS is promising with the intention to spare multi-visceral removal due to radical surgical resection. Therefore, there is a need to expand upon the molecular landscape of WDLPS and DDLPS which can help identify potential therapeutic targets for the treatment of this disease. Targeted transcriptome analysis using the NanoString tumor signaling 360 panel revealed a dysregulation in glucose metabolism and HIF1 signaling pathways in both WDLPS and DDLPS when compared to normal fat controls. WDLPS, however, demonstrated upregulation of HIF-1A and TGF-β when compared to DDLPS by targeted transcriptome analysis and orthogonal validation by RT-qPCR suggesting activation of EMT pathway in WDLPS when compared to DDLPS. Our findings implicate a putative role for dysregulation in glucose metabolism, TGF-β and HIF1 signaling in the pathogenesis of both WD/DDLPS suggesting a possible proinflammatory tumor environment within WDLPS and subsequent activation of the TGF-β signaling pathway.
Insights
Well-differentiated/dedifferentiated liposarcoma (WD/DDLPS) shows altered glucose metabolism and HIF1 signaling. WDLPS specifically exhibits increased HIF-1A and TGF-β, suggesting potential therapeutic targets for this common adult sarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Liposarcoma is the most common adult sarcoma, with well-differentiated/dedifferentiated liposarcoma (WD/DDLPS) being frequent subtypes.
- Current multimodality treatments offer limited survival benefits for WD/DDLPS, highlighting the need for novel therapeutic strategies.
- Understanding the molecular mechanisms driving WD/DDLPS is crucial for developing targeted therapies and improving patient outcomes.
Purpose of the Study:
- To investigate the molecular landscape of WD/DDLPS to identify potential therapeutic targets.
- To compare the molecular profiles of WDLPS and DDLPS to understand subtype-specific pathways.
- To explore the role of glucose metabolism, HIF1, and TGF-β signaling in liposarcoma pathogenesis.
Main Methods:
- Targeted transcriptome analysis using the NanoString tumor signaling 360 panel.
- Orthogonal validation of key gene expressions using RT-qPCR.
- Comparison of gene expression profiles between WD/DDLPS and normal adipose tissue.
Main Results:
- Both WDLPS and DDLPS exhibit dysregulation in glucose metabolism and HIF1 signaling pathways compared to normal fat.
- WDLPS shows significant upregulation of HIF-1A and TGF-β compared to DDLPS.
- Findings suggest activation of the epithelial-mesenchymal transition (EMT) pathway in WDLPS.
Conclusions:
- Dysregulation of glucose metabolism, TGF-β, and HIF1 signaling pathways are implicated in the pathogenesis of WD/DDLPS.
- WDLPS may possess a proinflammatory tumor environment with subsequent TGF-β pathway activation.
- These molecular alterations present potential targets for future precision medicine approaches in liposarcoma treatment.
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