GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients

eLife

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[1] Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden;Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden;Integrated Cardio Metabolic Centre (ICMC), Karolinska Institutet, Huddinge, Sweden;Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States;Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States;Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States;Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States;School of Molecular Sciences, University of Western Australia, Perth, Australia;Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States;Ahmanson Translational Imaging Division, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States;Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States;Jonsson Comprehensive Cancer Center (JCCC), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States;Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States;VIB-KU Leuven Center for Cancer Biology (CCB), Leuven, Belgium;VIB-KU Leuven Center for Cancer Biology (CCB), Leuven, Belgium;Max Delbrück Center for Molecular Medicine, Berlin, Germany;

关键词: endothelial cells;    lipoprotein lipase;    cancer metabolism;    lipolysis;    triglycerides;    NanoSIMS;    Human;    Mouse;   

DOI  :  10.7554/eLife.47178

来源: publisher

【 摘 要 】

10.7554/eLife.47178.001GPIHBP1, 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.

【 授权许可】

CC BY