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Updated: Jul 5, 2025
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Published on: July 5, 2018
Structural insight into CD93 recognition by IGFBP7
Yueming Xu1, Yi Sun2, Yuwen Zhu2
1Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
Abstract:
The CD93/IGFBP7 axis proteins are key factors expressed in endothelial cells (EC) that mediate EC angiogenesis and migration. Their upregulation contributes to tumor vascular abnormality and a blockade of this interaction promotes a favorable tumor microenvironment for therapeutic interventions. However, the interactions of these proteins with each other remain unclear. In this study, we determined a partial structure of the human CD93-IGFBP7 complex comprising the EGF1 domain of CD93 and the IB domain of IGFBP7. Mutagenesis studies confirmed interactions and specificities. Cellular and mouse tumor studies demonstrated the physiological relevance of the CD93-IGFBP7 interaction in EC angiogenesis. Our study provides leads for the development of therapeutic agents to precisely disrupt unwanted CD93-IGFBP7 signaling in the tumor microenvironment. Additionally, analysis of the CD93 full-length architecture provides insights into how CD93 protrudes on the cell surface and forms a flexible platform for binding to IGFBP7 and other ligands.
Insights
The CD93/IGFBP7 axis is crucial for endothelial cell (EC) angiogenesis. Blocking this interaction may improve cancer therapies by modulating the tumor microenvironment.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- The CD93/IGFBP7 axis in endothelial cells (EC) regulates angiogenesis and migration.
- Upregulation of these proteins contributes to abnormal tumor vasculature.
- Targeting this axis offers potential therapeutic strategies.
Purpose of the Study:
- To elucidate the interaction between CD93 and IGFBP7.
- To determine the structural basis of the CD93-IGFBP7 complex.
- To assess the physiological relevance of this interaction in EC angiogenesis and tumor models.
Main Methods:
- Partial structural determination of the human CD93-IGFBP7 complex.
- Mutagenesis studies to confirm interaction specificity.
- In vitro cellular assays and in vivo mouse tumor studies.
Main Results:
- A partial structure of the CD93-IGFBP7 complex (CD93 EGF1 and IGFBP7 IB domains) was determined.
- Mutagenesis confirmed specific interactions between these domains.
- The CD93-IGFBP7 interaction was shown to be physiologically relevant in EC angiogenesis within tumor models.
- Analysis of CD93 architecture provided insights into its cell surface presentation and ligand binding capabilities.
Conclusions:
- The CD93-IGFBP7 interaction is a key mediator of EC angiogenesis.
- Understanding this interaction provides a basis for developing targeted therapies against tumor angiogenesis.
- Further structural insights into CD93 aid in understanding its role as a signaling platform.
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