GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients-Reference-Cited by-同舟云学术

GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients

Published:2019-06-06 Issue: Volume:8 Page:
ISSN:2050-084X
Container-title:eLife
language:en
Short-container-title:

Author:

Hu Xuchen¹^ORCID,Matsumoto Ken²,Jung Rachel S¹,Weston Thomas A¹,Heizer Patrick J¹,He Cuiwen¹,Sandoval Norma P¹,Allan Christopher M¹,Tu Yiping¹,Vinters Harry V³,Liau Linda M⁴⁵,Ellison Rochelle M¹,Morales Jazmin E¹,Baufeld Lynn J⁶⁷,Bayley Nicholas A⁶⁷,He Liqun⁸,Betsholtz Christer⁸⁹,Beigneux Anne P¹,Nathanson David A⁶⁷,Gerhardt Holger²¹⁰^ORCID,Young Stephen G¹¹¹^ORCID,Fong Loren G¹^ORCID,Jiang Haibo¹¹²^ORCID

Affiliation:

1. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States

2. VIB-KU Leuven Center for Cancer Biology (CCB), Leuven, Belgium

3. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States

4. Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States

5. Jonsson Comprehensive Cancer Center (JCCC), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States

6. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States

7. Ahmanson Translational Imaging Division, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States

8. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

9. Integrated Cardio Metabolic Centre (ICMC), Karolinska Institutet, Huddinge, Sweden

10. Max Delbrück Center for Molecular Medicine, Berlin, Germany

11. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States

12. School of Molecular Sciences, University of Western Australia, Perth, Australia

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.

Funder

National Heart, Lung, and Blood Institute

Fondation Leducq

National Institutes of Health

National Institute of General Medical Sciences

National Cancer Institute

Stichting Tegen Kanker

Japan Society for the Promotion of Science

University of California, Los Angeles

Australian Research Council

Cancer Council Western Australia

Publisher