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The NG2 Proteoglycan in Pericyte Biology
1Tumor Microenvironment and Cancer Immunology Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. stallcup@sbpdiscovery.org.
Advances in Experimental Medicine and Biology
|December 8, 2018
Summary
The NG2 proteoglycan is crucial for blood vessel formation and function. Its absence impairs pericyte interactions, leading to deficits in tumor vascularization and growth.
Area of Science:
- Cell Biology
- Vascular Biology
- Cancer Research
Background:
- Pericyte identification and study were limited by a lack of specific markers.
- NG2 proteoglycan antibodies have enabled detailed investigation of pericytes and their role in vascularization.
Purpose of the Study:
- To elucidate the functional importance of NG2 proteoglycan in pericyte biology and blood vessel formation.
- To investigate the role of NG2 in tumor vascularization and growth.
Main Methods:
- NG2 knockdown (in vitro) and knockout (in vivo) strategies.
- Cre-Lox technology for pericyte-specific and myeloid-specific NG2 knockout mice.
- Analysis of tumor vascularization, pericyte-endothelial cell interactions, and macrophage recruitment.
Main Results:
- NG2 absence in pericytes significantly impairs blood vessel formation, proliferation, and motility.
- Pericyte-specific NG2 deficiency leads to defective tumor vessels with reduced ensheathment, basement membrane assembly, patency, and increased leakiness.
- Myeloid-specific NG2 deficiency causes greater tumor vascularization deficits, linked to impaired macrophage recruitment.
Conclusions:
- NG2 is essential for pericyte function, influencing endothelial cell signaling and vascular development.
- NG2 plays a critical role in tumor vascularization, with both pericyte-intrinsic and myeloid-derived functions.
- The interaction between pericytes, endothelial cells, and macrophages is vital for vascular homeostasis and tumor growth.
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