GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients

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. The 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 generating lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent in capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We document, by NanoSIMS imaging, 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.

Data availability

All data generated during this study are included in the manuscript and supporting files.

The following previously published data sets were used

Article and author information

Author details

  1. Xuchen Hu

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  2. Ken Matsumoto

    Vascular Patterning Lab, VIB-KU Leuven Center for Cancer Biology (CCB), Leuven, Belgium
    Competing interests
    No competing interests declared.
  3. Rachel S Jung

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  4. Thomas A Weston

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  5. Patrick J Heizer

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  6. Cuiwen He

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  7. Norma P Sandoval

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  8. Christopher M Allan

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  9. Yiping Tu

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  10. Harry V Vinters

    Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  11. Linda M Liau

    Department of Neurosurgery, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  12. Rochelle M Ellison

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  13. Jazmin E Morales

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  14. Lynn J Baufeld

    Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  15. Nicholas A Bayley

    Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  16. Liqun He

    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
    Competing interests
    No competing interests declared.
  17. Christer Betsholtz

    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
    Competing interests
    No competing interests declared.
  18. Anne P Beigneux

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  19. David A Nathanson

    Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  20. Holger Gerhardt

    Integrative Vascular Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany
    Competing interests
    Holger Gerhardt, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3030-0384
  21. Stephen G Young

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    For correspondence
    sgyoung@mednet.ucla.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7270-3176
  22. Loren G Fong

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    For correspondence
    lfong@mednet.ucla.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4465-5290
  23. Haibo Jiang

    Department of Medicine, University of California, Los Angeles, Los Angeles, United States
    For correspondence
    haibo.jiang@uwa.edu.au
    Competing interests
    No competing interests declared.

Funding

National Heart, Lung, and Blood Institute (HL090553)

  • Stephen G Young

National Heart, Lung, and Blood Institute (HL087228)

  • Stephen G Young

National Heart, Lung, and Blood Institute (HL125335)

  • Stephen G Young

Foundation Leduq (12CVD04)

  • Stephen G Young

Ruth L. Kirschstein National Research Service Award (T32HL69766)

  • Xuchen Hu

National Institute of General Medical Sciences (GM008042)

  • Xuchen Hu

NCI Brain Tumor SPORE (P50-CA211015)

  • Linda M Liau

Stichting Tegen Kanker (2012‐181)

  • Holger Gerhardt

Stichting Tegen Kanker (2018-074)

  • Holger Gerhardt

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Arun Radhakrishnan, University of Texas Southwestern Medical Center, United States

Ethics

Animal experimentation: Animal housing and experimental protocols were approved by UCLA's Animal Research Committee (ARC; 2004-125-51, 2016-005) and the Institutional Animal Care and Research Advisory Committee of the KU Leuven (085/2016). The animals were housed in an AAALAC (Association for Assessment and Accreditation of Laboratory Animal Care International)-approved facility and cared for according to guidelines established by UCLA's Animal Research Committee.

Human subjects: All tissue samples from patients were obtained after informed consent and with approval from the UCLA Institutional Review Board (IRB; protocol 10-000655).

Version history

  1. Received: March 27, 2019
  2. Accepted: June 5, 2019
  3. Accepted Manuscript published: June 6, 2019 (version 1)
  4. Version of Record published: June 26, 2019 (version 2)

Copyright

© 2019, Hu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Xuchen Hu
  2. Ken Matsumoto
  3. Rachel S Jung
  4. Thomas A Weston
  5. Patrick J Heizer
  6. Cuiwen He
  7. Norma P Sandoval
  8. Christopher M Allan
  9. Yiping Tu
  10. Harry V Vinters
  11. Linda M Liau
  12. Rochelle M Ellison
  13. Jazmin E Morales
  14. Lynn J Baufeld
  15. Nicholas A Bayley
  16. Liqun He
  17. Christer Betsholtz
  18. Anne P Beigneux
  19. David A Nathanson
  20. Holger Gerhardt
  21. Stephen G Young
  22. Loren G Fong
  23. Haibo Jiang
(2019)
GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients
eLife 8:e47178.
https://doi.org/10.7554/eLife.47178

Share this article

https://doi.org/10.7554/eLife.47178

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