Abstract
GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1-bound LPL is essential for the margination of triglyceride-rich lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. In peripheral tissues, the intravascular processing of TRLs by the GPIHBP1-LPL complex is crucial for the generation of lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent from the capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in the capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We use NanoSIMS imaging to show that TRLs marginate along glioma capillaries and that there is uptake of TRL-derived lipid nutrients by surrounding glioma cells. Thus, GPIHBP1 expression in gliomas facilitates TRL processing and provides a source of lipid nutrients for glioma cells.
Highlights
GPIHBP1, a GPI-anchored protein of capillary endothelial cells, is required for lipoprotein lipase (LPL)–mediated processing of triglyceride-rich lipoproteins (TRLs) [3]
Given the absence of GPIHBP1 expression in brain capillaries and the absence of TRL margination along brain capillaries, we have proposed that the LPL in the brain likely has an extravascular function, presumably to hydrolyze glycerolipids within the extracellular spaces [1, 2]
The expression of GPIHBP1 in glioma capillaries was intriguing, but the crucial issue is whether LPL would be bound to the GPIHBP1
Summary
GPIHBP1, a GPI-anchored protein of capillary endothelial cells, is required for lipoprotein lipase (LPL)–mediated processing of triglyceride-rich lipoproteins (TRLs) [3]. We sought to determine if glioma capillaries express GPIHBP1 and if so, whether it would bind LPL and facilitate TRL margination and lipolytic processing of TRLs. In our study, we took advantage of NanoSIMS imaging, a high-resolution mass spectrometry–based imaging modality that makes it possible to visualize TRL margination and TRL processing in. Hu et al Page 5 of 70 tissue sections [13, 36,37,38,39,40,41] This imaging modality allowed us to visualize TRL margination in glioma capillaries as well as the entry of TRL-derived nutrients into tumor cells
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