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CD31 Expression Determines Redox Status and Chemoresistance in Human Angiosarcomas
Vivek Venkataramani1,2, Stefan Küffer3, Kenneth C P Cheung4
1Department of Hematology and Medical Oncology, University Medical Center Göttingen (UMG), Göttingen, Germany. ramani@med.uni-goettingen.de.
Summary
Human angiosarcomas contain aggressive CD31-low cells resistant to chemotherapy. Inhibiting YAP signaling can resensitize these cells, offering new therapeutic strategies for angiosarcoma treatment.
Area of Science:
- Oncology
- Cell Biology
- Molecular Medicine
Background:
- Angiosarcomas are malignant vascular tumors.
- CD31/PECAM-1 is highly expressed in angiosarcomas, but its function is unclear.
- Understanding CD31's role is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the biological function of CD31 in angiosarcoma.
- To determine the role of CD31 in chemoresistance and tumorigenicity.
- To explore YAP signaling in CD31-mediated angiosarcoma aggressiveness.
Main Methods:
- Analysis of CD31 expression in human angiosarcoma samples and cell lines.
- Isolation and characterization of CD31high and CD31low cell subsets.
- Utilizing CD31-blocking antibodies, siRNA, and CD31-knockout models to study redox and YAP signaling.
Main Results:
- Angiosarcomas harbor a CD31low population with reduced endothelial properties and increased tumorigenicity.
- CD31low cells exhibit enhanced chemoresistance via superior reactive oxygen species (ROS) detoxification.
- Downregulation of CD31 promotes YAP signaling, leading to increased antioxidative capacity.
Conclusions:
- A subset of aggressive, chemoresistant CD31low angiosarcoma cells exists, characterized by diminished endothelial differentiation and heightened YAP activity.
- Targeting YAP signaling, potentially with YAP inhibitors like pazopanib, can resensitize CD31low cells to doxorubicin.
- These findings pave the way for novel combination therapies against angiosarcomas.
